# ent

id: cord-000149-dp8971im
type: DNA
entity:
  generic class I primers 5 GGACTCA G A A T C T C C C C A G A C G C C G A G a n d 3 TCTCAGTCCCTCACAAGGCAGCTGTC


id: cord-000871-ej0e1c4d
type: WORK_OF_ART
entity:
  Mapping the Landscape of Host Pathogen Coevolution HLA Class I Binding and Its Relationship with Evolutionary Conservation in Human and Viral Proteins Jump


id: cord-000871-ej0e1c4d
type: WORK_OF_ART
entity:
  Mapping the Landscape of Host Pathogen Coevolution HLA Class I Binding and Its Relationship with Evolutionary Conservation in Human and Viral Proteins Comparison of Site Specific Rate Inference Methods for Protein Sequences Empirical Bayesian Methods


id: cord-000871-ej0e1c4d
type: DISEASE
entity:
  Human Immunodeficiency Virus Type 1 HIV 1 Proteins Reveal Imprints of Immune Evasion on HIV 1 Global Variation Human T cell


id: cord-000479-u87eaaj8
type: PROTEIN
entity:
  58 kD GRP58 NF kB Factor nuclear kappa B AP 1 Activator protein 1 STAT 3 Signal transducer and activator of transcription 3


id: cord-013315-plptulfb
type: PROTEIN
entity:
  proteins Malate dehydrogenase P61976 Uncharacterized oxidoreductase MAP_3007 Q73VK6 and hypothetical protein EGA31_12440


id: cord-013315-plptulfb
type: WORK_OF_ART
entity:
  the Proteasome Pathogenesis of Bacterial Infections in Animals Membrane and Cytoplasmic Proteins of Mycobacterium


id: cord-007851-v6h1yro7
type: CHEBI
entity:
  amino acid binding motifs and sequence profiles including sequence weighting pseudo counts and two sided representation of amino acid


id: cord-007851-v6h1yro7
type: ORG
entity:
  Peptide Based Vaccination for Antibody Responses Against HIV Vaccines Basel Immunologic Response Elicited in Breast Cancer Patients Receiving a NeuGcGM3


id: cord-007851-v6h1yro7
type: WORK_OF_ART
entity:
  A Prognostic Model for Patients with Triple Negative Breast Cancer Importance of the Modified Nottingham Prognostic Index and Age Triple


id: cord-007851-v6h1yro7
type: WORK_OF_ART
entity:
  Assessment of Antigen Specific Cellular Immunogenicity Using Intracellular Cytokine Staining ELISpot and Culture Supernatants


id: cord-013590-pkm81fq1
type: PROTEIN
entity:
  antigen presenting molecule MR1 Cell stress regulated human major histocompatibility complex class I gene


id: cord-013590-pkm81fq1
type: CHEMICAL
entity:
  gamma delta T cell receptor on intestinal CD8 intraepithelial lymphocytes Homing of a gamma delta thymocyte subset


id: cord-007275-emmoeuqd
type: GGP
entity:
  B2m þ þ female 3 B2m þ þ male 43 6 2 315 6 10 B2m À À female 3 B2m À À male 31 6 4 147 6 7 B2m À À female 3 B2m þ þ male 34 6 6 134 6 6 B2m þ þ female 3 B2m À À male 35 6 7 124 6 9 B2m À þ female 3 B2m À þ


id: cord-008523-avkgldnp
type: PROTEIN
entity:
  B10 A 18R mice even though the background of this strain may be favorable for the selection of CTL escape mutants 6 MHV JHM


id: cord-003270-vu9b5a14
type: PROTEIN
entity:
  epitopes 109 FAFRDLCIVY 110 CYSLYGTTL 111 VYDFAFRDL 111 112 KFYSKISEY 113 KLPQLCTEL 114 115 116 ISEYRHYCY 117 EYRHYCYSL 111 KLPDLCTEL 116 118 119 120 FAFKDLFVV 119 120


id: cord-021693-odfxkfu7
type: DISEASE
entity:
  herpes simplex virus adenovirus human papillomavirus Epstein Barr virus influenza type A virus reovirus type 3


id: cord-007654-lchdm4xr
type: CELL_LINE
entity:
  Semliki Forest virus RNA synthesis 100 11 of 1 20 dilution of supernatants from 48 h WNV B infected astrocytes


id: cord-007654-lchdm4xr
type: DISEASE
entity:
  herpes simplex virus type 1 and 2 on surface expression of class major histecompatibility complex antigens on infected cells Antigen inducible H 2


id: cord-004518-jd1wxobz
type: GGP
entity:
  Warsz DOI 10 1007 s00005 007 0044 4 sha d6961703fbc4b3305ec67e5458cfb9ff76a885ba doc_id 4518 cord_uid jd1wxobz Vaccination is historically one of the most


id: cord-004518-jd1wxobz
type: DISEASE
entity:
  cancers hepatocellular carcinoma renal cell carcinoma pancreatic cancer chronic lymphocytic leukemia breast cancer ovarian cancer prostate cancer bladder cancer synovial sarcoma leiomyosarcoma lung cancer


id: cord-000224-2lz03oqb
type: PROTEIN
entity:
  nonpolymorphic and polymorphic antibody binding epitopes Macrophage tropic human immunodeficiency virus isolates


id: cord-000224-2lz03oqb
type: FAC
entity:
  Their Plasma Membrane by Oligoubiquitination Human Immunodeficiency Virus 1 Nef Expression Induces Intracellular Accumulation of Multivesicular Bodies


id: cord-000224-2lz03oqb
type: WORK_OF_ART
entity:
  The Acquisition of Host Derived Major Histocompatibility Complex Class II Glycoproteins by Human Immunodeficiency Virus


id: cord-000224-2lz03oqb
type: WORK_OF_ART
entity:
  Accelerates the Process of Virus Entry and Infection in Human T Lymphoid Cells Identification of CIITA


id: cord-000224-2lz03oqb
type: ORG
entity:
  Gut Mucosal Immune Function Updates on Pathogenesis with Implications for Management and Intervention Characteristics


id: cord-000224-2lz03oqb
type: DISEASE
entity:
  Human Immunodeficiency Virus Type 1 RNA Dimerization and Viral Infectivity The Human Immunodeficiency Virus Type 1 Ribosomal Frameshifting


id: cord-003472-ml4pbewf
type: DNA
entity:
  assoc drb1 12 02 assoc drb1 1202 assoc drb1 12 01 assoc drb1 1201 assoc dr12 assoc drb1 12 assoc drb1 03 01 assoc drb1 0301 assoc dr3 assoc drb1 03 assoc dr17 infect drb1 12 02 infect drb1 1202 infect drb1 12 01 infect drb1 1201 infect dr12 infect drb1 12 infect drb1 03 01 infect drb1 0301 infect dr3 infect drb1 03


id: cord-003472-ml4pbewf
type: DNA
entity:
  NetMHCpan 4 0 Improved Peptide MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data Deriving phylogenetic trees


id: cord-001674-tp4o7fxx
type: DISEASE
entity:
  Bacillus subtilis signal peptide peptidase A Structure of signal peptide peptidase A with C termini bound in the active


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  Protein Kinase C Methoden Leberzirrhose bei Ratten wurde durch Gallengangsligatur BDL induziert Isolierte Aorten wurden in vitro mit bzw ohne Angiotensin II


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  G Protein abhängiger Signalwege unter normalen Umständen z B Kontraktions Kaskaden werden bei Leberzirrhose b Arrestin 2


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  wurde durch Bestimmung von PARP Caspase 8 und 9 Spaltprodukten sowie mittels TUNEL Reaktion untersucht Ergebnisse Transfektion von Huh7 5 Zellen mit Replikations kompetenter JFH 1 nicht jedoch mit Replikations defizienter JFH 1 GND RNA führte zu einer Apoptose von Huh7 5 Zellen nachgewiesen


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  Ergebnisse Die Inkubation von AR4 2J Zellen mit Bier 1 10 v v bewirkte eine dosisabhängige Stimulation der


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  BNP Konzentrationen mit dosisabhängigen Senkungen von 26 p 0 1 30 p 0 05 und 38 p 0 01 gegenüber Placebo für


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  Schlagvolumens von 6 9 16 ml Die Methode zeigte eine gute Reproduzierbarkeit mit einer mittleren Abweichung von 0 1 0 5


id: cord-005953-5z89yeb6
type: PROTEIN
entity:
  I II III IV 94 92 88 85 und der GAI 5 94 91 72 72 p für Trend jeweils 0 001 Die Therapie Adhärenz GAI 3


id: cord-005953-5z89yeb6
type: GGP
entity:
  animals n 6 p 0 05 Discussion In summary we demonstrated that under basline conditions conditional transgenic


id: cord-005953-5z89yeb6
type: GGP
entity:
  hOCT1 0 4 1 μmol l Mittelwert Standardfehler OCT2 3 8 1 Nelfinavir 7 1 33 11 Ritonavir 14 2 51 22 Lamivudine 17 3 13 3 Trimethoprim 20 3 131 12 Zalcitabine 24 5 25 7 Saquinavir 37 7 105 29 und Indinavir 37 6 275 57 zeigten eine signifikante Hemmung von OCT1 2 Lamivudine


id: cord-005953-5z89yeb6
type: DISEASE
entity:
  frisch isolierter Pankreasazinuszellen der Ratte A Gerloff 1 M V Singer 1 P Feick 1 1 II Medizinische Klinik Universitätsklinikum Mannheim Mannheim Hintergrund Da der


id: cord-005953-5z89yeb6
type: CHEMICAL
entity:
  sind kann indirekt geschlossen werden dass unsere stationäre Rehabilitationsstrategie langfristig positive Effekte


id: cord-005953-5z89yeb6
type: CHEMICAL
entity:
  Patienten A Viktor 1 I Tuleta 2 M Steinmetz 2 G Bauriedel 3 G Nickenig 2 D Skowasch 2 1 Abteilung für Kardiologie


id: cord-005953-5z89yeb6
type: DISEASE
entity:
  Neueinstellung mit dem Wirkstoff Valsartan zeigte nach 28 Tagen eine signifikant reduzierte Kollagen induzierte Plättchenaggregation 36 p 0 006 Eine


id: cord-022395-rk31pwoa
type: DISEASE
entity:
  human immunodeficiency virus and peptides from HIV 1 envelope glycoproteins Interleukin 1 stimulates the release


id: cord-277054-eq4obbte
type: DISEASE
entity:
  HIV type 1 uninfected adults Phase I clinical trial safety of DNA and modified virus Ankara vectored human immunodeficiency virus type 1 HIV 1 vaccines administered alone


id: cord-264401-9ogs55xr
type: PROTEIN
entity:
  Neotropic bat family Phyllostomidae Sturnira lilium and Artibeus planirostris in several countries of Central and South America Figure 1 Tong et al 2012 Tong et al 2013 Campos et al 2019 Influenza A viruses IAVs


id: cord-267266-0lybzcz7
type: PROTEIN
entity:
  intercellular adhesion molecule ICAM 1 CD54 ICAM 3 CD50 leucocyte functional antigen LFA 3 CD58 B7 1 CD80


id: cord-267266-0lybzcz7
type: CELL_TYPE
entity:
  haemopoietic cells DC dendritic cell ICAM intercellular adhesion molecule 1 LFA leucocyte functional antigen Dendritic cell


id: cord-017296-jdp8kgg5
type: CELL_TYPE
entity:
  G CSF peripheral blood stem cell transplantation PBSCT Cryopreserved umbilical cord blood stem cells


id: cord-017296-jdp8kgg5
type: DNA
entity:
  T cell repertoire Def Def Meth Meth Immunotherapy Proteins e g melanoma antigens tyrosinase MAGE 1 3 Melan A


id: cord-017296-jdp8kgg5
type: PROTEIN
entity:
  growth factor Transforming growth factors TGFα TGFβ tumor necrosis factor alpha TNFα Interleukin Integrins


id: cord-017296-jdp8kgg5
type: DISEASE
entity:
  somatic cell and gene therapy Suspension culture using unseparated or CD34 separated stem cells advantage of reduced culture volume Addition of recombinant growth factors Optimal cytokine combinations


id: cord-017296-jdp8kgg5
type: DISEASE
entity:
  bone marrow reconstitution bacterial infections fungal infections Candida Aspergillus viral infections


id: cord-281691-3tl7f6tt
type: CELL_LINE
entity:
  human HLA mouse H 2 mouse MHC macaque MAMU macaque MHC chimpanzee PATR chimpanzee MHC horse ELA equine leucocyte antigen


id: cord-013093-aa4cf44u
type: CELL_LINE
entity:
  BD Biosciences CD4 PE Texas Red clone S3 5 MHCD0417 CD45RA Qdot 655 clone MEM 56 Q10069 CD95 PerCP eFluor 710 clone DX2 46 0959 42


id: cord-013093-aa4cf44u
type: ORG
entity:
  Mass Spectrometry Enhances Cancer Epitope Prediction Is It Possible to Develop a Universal Influenza Virus Vaccine Outflanking Antibody Immunodominance


id: cord-304635-z5vmhopa
type: ORG
entity:
  the Committee on the Ethics of Animal Experiments of National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention Mice


id: cord-304635-z5vmhopa
type: ORG
entity:
  National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention


id: cord-304635-z5vmhopa
type: DISEASE
entity:
  acute respiratory syndrome coronavirus CD8 T cell epitope Hemagglutininspecific CD4 T cell responses


id: cord-279924-09uwhxs9
type: PROTEIN
entity:
  rabbit monoclonal anti Sox2 Epitomics and Alexa Fluor 568 goat anti rabbit IgG 1 secondary antibody Life


id: cord-279924-09uwhxs9
type: CELL_LINE
entity:
  EasySep Mouse T Cell Isolation kit Stemcell technologies This enriched fraction was treated with 50 μg mL mitomycin C AG Scientific and 35 Â 10 6 cells


id: cord-279924-09uwhxs9
type: GGP
entity:
  NPCs 2 6 Â 10 5 75 4 Â 10 4 PFU mL Under normal culture conditions expression of MHC classes I and II


id: cord-298169-2133gahl
type: ORG
entity:
  schizophrenia Structural Magnetic Resonance Imaging Demonstrates Abnormal Regionally Differential Cortical Thickness Variability


id: cord-291070-y0wf456f
type: PROTEIN
entity:
  BALB c mouse date 2005 07 01 journal Nucleic Acids Res DOI 10 1093 nar gki479 sha 47e5a99b14df794d9c33c1b1e8ff258d3f89a1d2 doc_id 291070 cord_uid y0wf456f PRED BALB c


id: cord-291070-y0wf456f
type: ORG
entity:
  the National Institute of Allergy and Infectious Diseases National Institutes of Health Department of Health and Human Services


id: cord-275608-joyan7ij
type: SO
entity:
  part of the antigen receptor and are largely responsible for the diversity in these molecules The CDRs


id: cord-283035-tpqf458q
type: PROTEIN
entity:
  NKEF eukaryotic elongation factor 2 EEF2 aldolase B ALDOB membrane associated guanylate kinase MAGI3


id: cord-283035-tpqf458q
type: CL
entity:
  Mannheimia haemolytica virulence factor expression A statistical model for identifying proteins by tandem mass spectrometry Marek s disease virus


id: cord-306096-2yl07bdq
type: DISEASE
entity:
  herpes simplex cytomegalovirus Epstein Barr virus vaccinia virus myxoviruses paramyxoviruses arenaviruses flaviviruses orthoviruses rhabdoviruses coronaviruses


id: cord-023055-ntbvmssh
type: CELL_TYPE
entity:
  multicellular dendritic cell CD4 T cell clusters Cellular Immunology 111 183 195 1988 Dendritic cells


id: cord-023055-ntbvmssh
type: CELL_LINE
entity:
  T cell clones Jayne S Danska Alexandra M Livingstone Toshi Isihara and C Garrison Fathman Stanford University Medical School Stanford CA


id: cord-023055-ntbvmssh
type: PROTEIN
entity:
  CD4 CD8 THYMOCYTES Mark W Moore I Nicholas Crispe and Michael J Bevan Department of Immunology Research Institute of Scripps Clinic La Jolla CA 92037 The role of TCR 7 genes


id: cord-023055-ntbvmssh
type: CELL_LINE
entity:
  T cell hybridomas D Bloom P L Cohen and S H Clarke Department Medical Institute and Experimental Immunology Branch NCI NIH Bethesda MD 20892


id: cord-023055-ntbvmssh
type: ORG
entity:
  Prystowsky Department of Pathology and Laboratory Medicine University of Pennsylvania Philadelphia PA


id: cord-299786-wuve0tjz
type: PROTEIN
entity:
  intercellular adhesion molecule 1 ICAM 1 CD54 vascular cell adhesion molecule 1 VCAM 1 CD106 and E selectin


id: cord-299786-wuve0tjz
type: CELL_LINE
entity:
  human lymphoblastoid lines Japanese encephalitis virus up regulates expression of macrophage migration inhibitory factor MIF mRNA


id: cord-308043-h0knm8y4
type: PROTEIN
entity:
  mammalian autophagy proteins ULK1 Unc 51 like kinase FIP200 focal adhesion kinase family interacting protein


id: cord-319761-bu5pzbnv
type: PROTEIN
entity:
  paramyxoviruses simian virus 5 and human parainfluenza virus type 2 Latency associated nuclear antigen


id: cord-319761-bu5pzbnv
type: DISEASE
entity:
  adenovirus Epstein barr virus EBV BHRF1 protein and other viruses 17 18 There are several classes of caspase inhibitors


id: cord-310194-f5jtufja
type: DNA
entity:
  bovine isotype specific mouse monoclonal antibodies 19 and FITC conjugated polyclonal goat anti mouse antibodies BD Biosciences Total leukocytes


id: cord-310252-0cdqhrcw
type: CHEMICAL
entity:
  IFN interferon IFN R1 interferon receptor 1 IL interleukin IRF interferon regulatory factor ISG interferon stimulated genes ISGF3 IFN


id: cord-334603-yt2pmxi3
type: DNA
entity:
  human alpha beta T cell receptor TCR HA1 7 influenza hemagglutinin peptide and major histocompatibility complex class II molecule HLA DR4 DRA 0101


id: cord-334603-yt2pmxi3
type: ORG
entity:
  SARS CoV 2 National Science Review TepiTool A Pipeline for Computational Prediction of T Cell Epitope Candidates


id: cord-023143-fcno330z
type: GGP
entity:
  e i t h e r U S 1 1 o r US2 6 gene products s i g n i f i c a n t l y reduced l e v e l s of MHC class I heavy chain


id: cord-023143-fcno330z
type: ORG
entity:
  CNS encephalomyelitis Division of Retrovirology Walter Reed Army Institute of Research and Henry M Jackson Foundation


id: cord-023143-fcno330z
type: DISEASE
entity:
  T cell recognition Investigations of the characteristics of the enzymes contributing to the degradation of the Gpt have shown that a reducing environment is essential as diamide treatment


id: cord-329036-4bf8eiix
type: DNA
entity:
  rat monoclonal anti mouse IFN 3 antibody hybridoma R4 6A2 ATCC HB 170 or rabbit polyclonal anti mouse IFN a 3 Lee Biomolecular


id: cord-313138-y485ev30
type: GGP
entity:
  Comp Immunol DOI 10 1016 j dci 2013 04 010 sha c8f7838853a28b0618da802dd333f6eeaa1f5fe8 doc_id 313138 cord_uid y485ev30 Birds


id: cord-313138-y485ev30
type: GGP
entity:
  IFIT5 XM_003208028 1 zebra finch IFIT5 XM_002188552 1 human IFIT1 NM_001270927 1 mouse IFIT1 NM_008331 3 human IFIT2


id: cord-313138-y485ev30
type: GGP
entity:
  avian Toll like receptor TLR system implications for transmission and control of bird borne zoonoses The LILR family modulators of innate and adaptive immune


id: cord-322575-3goj00ej
type: ORG
entity:
  the National Institute of Allergy and Infectious Diseases National Institutes of Health and Harlan Laboratories


id: cord-322575-3goj00ej
type: ORG
entity:
  the National Institute of Allergy and Infectious Diseases National Institutes of Health and Harlan Laboratories Inc


id: cord-296347-fanlvxqs
type: CL
entity:
  autocrine motility factor receptor AMFR Nabi et al 1992 and later as an E3 ligase due to its homology to Hrd1p and


id: cord-296347-fanlvxqs
type: CHEMICAL
entity:
  N linked glycans in the endoplasmic reticulum Proteasomes A complex story Interference with antigen processing by viruses A viral ER


id: cord-335342-u0ys2xcm
type: CELL_LINE
entity:
  murine NSCLC cell line CMT 64 human MAA human small cell lung carcinoma human squamous cell carcinoma


id: cord-340781-z348xbn0
type: PROTEIN
entity:
  L1 protein L1 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 EATVYLPPVPVSKVV type16 L1 408 421 PPPGGTLEDTYRFV type16


id: cord-340781-z348xbn0
type: DNA
entity:
  L2 protein L2 22 23 24 25 26 27 28 29 30 31 32 33 34 35 KQSGTCPPDVVPKV type18 L2 100 113 PSDPSIVSLVEETS type16 L2 94 107


id: cord-340781-z348xbn0
type: RNA
entity:
  L1 12 13 14 15 16 17 18 19 20 21 YLPPVPVSKV type 16 and YLPPPSVARV type 18 L1 460 470 DQFPLGRKFLL type 16 L1 461 471 DQYPLGRKFLV type 18 L2 11 12 13 14 15 16 17 18 19 20 KRASATQLYK type 16


id: cord-340781-z348xbn0
type: PROTEIN
entity:
  epitopes L1 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 EATVYLPPVPVSKVV type 16 L1 95 111 TQRLVWACVGVEVGRGQ type 16


id: cord-340781-z348xbn0
type: DNA
entity:
  L1 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 L1 408 421 L1 404 417 L2 22 35 L2 100 113 L2 94 107 and L2 57 70


id: cord-353877-wzndpcq3
type: DNA
entity:
  MHC I alleles HLA A 02 01 HLA B15 03 HLA C 12 03 and MHC II alleles HLA DPA1 01 03 DPB1 02 01 HLA DQA1 01 02 DQB1 06 02 HLA DRB1


id: cord-353877-wzndpcq3
type: GGP
entity:
  AllergenFP v 1 0 22 AllerCatPro 23 v 1 7 ToxinPred 24 servers The result showed that all the peptides


id: cord-350772-fp5d9if0
type: CELL_LINE
entity:
  PerCP clone 30 F11 BD Biosciences San Jose CA and PE conjugated anti MHC Class I clone 28 14 8 eBioscience San Diego CA


id: cord-352150-ey9kc7zj
type: ORG
entity:
  Cross Reactivity of TCR Repertoire Current Concepts Challenges and Implication for Allotransplantation


id: cord-347298-7kqrl3rv
type: GGP
entity:
  nitric oxide synthase TNF tumor necrosis factor IL interleukin IL1ra interleukin 1 receptor antagonist


id: cord-350583-0t1kly3i
type: PROTEIN
entity:
  amino 1 domain position 9 11 14 26 28 30 37 47 57 66 70 74 78 85 90 Alignment Position 1 10 20 30 40 50 55 58 60 70 80 68


id: cord-354030-8tfg881h
type: PRODUCT
entity:
  I99 G100 C102 S103 M104 T105 D106 I107 A108 K109 K110 P111 T112 E113 T114 I115 C116 A117 P118 L119 T120 G125 R126 V127 D128 G129 V131 D132 L133 F134 R135 N136


id: cord-355075-ieb35upi
type: PROTEIN
entity:
  ISGs myxovirus resistance Mx GTPases Protein kinase R PKR 2 5 oligoadenylate synthetases OAS ribonuclease L RNaseL


id: cord-355075-ieb35upi
type: ORG
entity:
  Chicken Is Characterized by Massive Expansion and Diversification of Immunoglobulin Like Loci The Chicken Leukocyte Receptor


id: cord-009567-osstpum6
type: PROTEIN
entity:
  DCs CD11c 18mths vs 3mths CD4 2 77 vs 1 35 CD8 3 90 vs 1 71 CD11c 46 1 vs 11 8 p 0 05 Following engraftment of 18mths


id: cord-009567-osstpum6
type: PROTEIN
entity:
  Lymphocyte Function Associated Antigen LFA 1 CD11a Intercellular Adhesion Molecule ICAM 1 CD54 Selectin E CD62E Selectin P CD62P VE


id: cord-009567-osstpum6
type: CELL_LINE
entity:
  137 bronchoalveolar lavage BAL mRNA samples 3 8 per LTx patient by Real Time PCR for GZMB IFN γ IL 15 MCP 1 RANTES TNF


id: cord-009567-osstpum6
type: DNA
entity:
  Ev and Cs gr 95 2 and 86 6 vs 87 5 and 87 5 respectively p ns Causes of death were sepsis 1 HCV recurrence 1 pulmonary embolism 1


id: cord-009567-osstpum6
type: CELL_LINE
entity:
  MPA Nonstimulated cells 0 249 0 28 Stimulated cells 0 391 0 33 MPA treated stimulated cells 0 279 0 43 p 0 0005


id: cord-009567-osstpum6
type: DNA
entity:
  1 and 5 years ATG 1 4 0 6 mg dl and 1 4 0 8 mg dl vs basiliximab 1 3 0 7 mg dl and 1 5 0 9 mg dl Patients


id: cord-009567-osstpum6
type: PROTEIN
entity:
  FOXP3 CD4 CD25 Natural Regulatory T nT reg Cells Guliang Xia 1 Jie He Methods Fresh naive CD4 CD25 nT reg


id: cord-009567-osstpum6
type: DNA
entity:
  OPTN UNOS Database Suphamai Bunnapradist 1 Steven Takemoto 2 Jagbir Gill 1 Tariq Shah 2 1 Medicine Nephrology UCLA LA CA 2 Medicine Nephrology National Institute of Transplantation LA CA


id: cord-009567-osstpum6
type: GGP
entity:
  Antigen LFA 1 CD11a Intercellular Adhesion Molecule ICAM 1 CD54 Selectin E CD62E Selectin P CD62P VE Cadherin CD144 Human Leukocyte Antigen HLA II DP DQ DR Psoriasin


id: cord-009567-osstpum6
type: GGP
entity:
  cytokines IL 6 IL 1R α 2 folds IL 1 β IL 13 20 folds IL 10 2 folds decrease chemokines IL 8 MCP1 2 4


id: cord-009567-osstpum6
type: GGP
entity:
  Quintini 1 L Kauzman 1 K Hashimoto 1 P Ding 1 T Doago Uso 1 N Sopko 1 J Rosenblum 1 F Aucejo 1 C Winans 1 D Kelly 1 B Eghtesad 1 D Vogt 1


id: cord-009567-osstpum6
type: CL
entity:
  basal 2 5 0 9 vs 24 hours 8 1 3 6 p 0 02 In conclusion our results suggest that kidney transplant recipients with DGF present a bias toward a Th1 driven immune response both at the peripheral and at the tissue level This event due to the I R process as suggested by the animal


id: cord-009567-osstpum6
type: CHEBI
entity:
  amino acid 2 5g kg day p 0 00 days of lipid 2 5 g kg day p 0 00 and total days of PN p 0 00 The final multiple variable model which had a negative predictive value of 97 6 and positive predictive value of 52 6 is presented in the table below Our model suggests a key role of PN lipids


id: cord-009567-osstpum6
type: ORG
entity:
  Nephrology University of Heidelberg 2 Transplantation Immunology University of Heidelberg 3 Transplantation Surgery University of Heidelberg 4 Endocrinology University of Heidelberg


id: cord-009567-osstpum6
type: ORG
entity:
  Starzl Transplantation Institute Dept of Surgery University of Pittsburgh Pittsburgh PA 2 Immunology University of Pittsburgh Pittsburgh PA


id: cord-009567-osstpum6
type: ORG
entity:
  Composite Tissue Allotransplantation Investigation of the Immunomodulatory Phenotype of Infiltrating Lymphozytes in Skin Rejection of Human


id: cord-009567-osstpum6
type: WORK_OF_ART
entity:
  Inflammatory Bowel Disease Course in Patients Transplanted for Primary Sclerosing Cholangitis Ariana


id: cord-009567-osstpum6
type: PRODUCT
entity:
  Liver Non Parenchymal Components Inhibit Dendritic Cell Differentiation and Maturation Ching Chun Hsieh 1 Horng


id: cord-009567-osstpum6
type: WORK_OF_ART
entity:
  Antibody Production and Antigen Presentation Are Directly Inhibited by Mycophenolate Mofetil Anat R Tambur 1


id: cord-009567-osstpum6
type: ORG
entity:
  School Boston MA 2 Department of Pathology Massachusetts General Hospital Harvard Medical School Boston MA


id: cord-009567-osstpum6
type: DISEASE
entity:
  liver allograft intra abdominal other than liver biliary cardiac pulmonary neurologic sepsis renal and endocrine


id: cord-009567-osstpum6
type: CHEMICAL
entity:
  Mycophenolate Mofetil Anat R Tambur 1 Joe Leventhal 1 Nancy D Herrera 1 Joshua Miller 1 1 Division of Organ Transplantation


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  multimeric LPS receptor complex L Lundvall 1 R R Schumann 1 1 Charité Universitätsmedizin Berlin Campus Mitte Institute for Microbiology and Hygiene Berlin Germany Meningitis


id: cord-022888-dnsdg04n
type: CELL_TYPE
entity:
  Tcell subsets S M Lehmann 1 D Kaul 1 C Krüger 1 F Zipp 1 R Nitsch 2 S Lehnardt 1 1 Charité Universitätsmedizin Berlin Cecilie Vogt Clinic


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  anti inflammatory nuclear transcription factor Peroxisome Proliferator Activated Receptor gamma PPARg


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  HSV1 infected macrophage secretome H P Prakash 1 2 1 German Cancer Research Centre Translational Immunology Heidelberg Germany 2 Max Planck


id: cord-022888-dnsdg04n
type: CELL_LINE
entity:
  24abNKT cell transgenic mice Results In 24ab transgenic mice a high frequency of activated transgenic NKT cells


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  cytokine receptors IL 2Ra IL 2Rg IL 3 IL 5 GM CSFR IL 4 IL 13R IL 5Ra IL 6Ra IL 6R gp130 IL 7Ra IL 10R TNFR I TNFR II IFNgRa CXCR1 CXCR2 CXCR3 CXCR4 CXCR5 Cells


id: cord-022888-dnsdg04n
type: DNA
entity:
  e 9 2 phosphonomethoxy ethlyl 2 6 diaminopurine derivatives c 9 2 hydroxy 3 phosphonomethoxy propyl adenine HPMPA


id: cord-022888-dnsdg04n
type: CELL_TYPE
entity:
  thymic T cell tumors S Myrczek 1 R Pardi 2 A Gessner 1 1 Microbiological Institute Institute for Clinical Microbiology Immunology and Hygiene University Hospital Erlangen Erlangen Germany 2 Vita Salute San


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  antibodies A Giniewski 1 S Lang 1 M Stein 1 T Winkler 1 1 Friedrich Alexander University Erlangen Germany VDJ recombination


id: cord-022888-dnsdg04n
type: CELL_TYPE
entity:
  antigen specific T cells S J Keppler 1 P Aichele 1 1 IMMH University Freiburg Immunology Freiburg Germany Interleukin 12 IL 12


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  carboxy terminal region L Kolly 1 S Narayan 1 J Tschopp 2 A So 1 N Busso 1 1 CHUV Rheumatology Lausanne Switzerland 2 UNIL


id: cord-022888-dnsdg04n
type: CELL_TYPE
entity:
  mature human B cells S Gutenberger 1 K Warnatz 1 1 University Medical Centre Freiburg Freiburg Germany Background


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  recombinant vaccinia virus recombinant VSV vesicular stomatitis virus or recombinant listeria monocytogenes expressing LCMV glycoprotein P14 T cells


id: cord-022888-dnsdg04n
type: CELL_TYPE
entity:
  P14 T cells S Frischbutter 1 R Baumgrass 1 1 Deutsches Rheuma Forschungszentrum Signal Transduction Berlin Germany Antigen


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  L selectin V Heissmeyer 1 E Glasmacher 1 1 Helmholtz Center Munich Molecular Immunology Munich Germany During self antigen recognition Roquin dependent posttranscriptional downregulation of ICOS


id: cord-022888-dnsdg04n
type: DNA
entity:
  promoters S Brosch 1 S Tenzer 1 H Schild 1 E von Stebut Borschitz 1 1 Uniklinik Mainz Mainz Germany Infection


id: cord-022888-dnsdg04n
type: DNA
entity:
  J Kyosiimire Lugemwa 1 2 P Pala 1 G Miiro 3 J Todd 3 P Kaleebu 1 2 N Imami 2 F Gotch 2 3 1 MRC Uganda Basic Science Entebbe Uganda 2 Imperial College London United Kingdom 3 MRC Uganda Entebbe Uganda Background HIV 1


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  CD4 G Röder 1 L Geironson 2 A Darabi 3 M Harndahl 1 C Schafer Nielsen 4 K Skjödt 5 S Buus 1 K Paulsson 2 1 Copenhagen University Institute of International Health Immunology and Microbiology Department of Experimental Immunology Copenhagen Denmark 2 Lund University Immunology BMC D14 Lund Sweden 3


id: cord-022888-dnsdg04n
type: PROTEIN
entity:
  anti TT antibody formation 2 kDa 30 6 kDa 23 9 kDa 19 8 9 10 11 12 13 14 15 16 17 18 19 20 6 kDa and 18 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 7 kDa


id: cord-022888-dnsdg04n
type: GGP
entity:
  cytokine receptors IL 2Ra IL 2Rg IL 3 IL 5 GM CSFR IL 4 IL 13R IL 5Ra IL 6Ra IL 6R gp130 IL 7Ra IL 10R TNFR I TNFR II


id: cord-022888-dnsdg04n
type: GGP
entity:
  inositol 1 4 5 trisphosphate 3 kinase type B ITPKB phosphorylates Inositol 1 4 5 trisphosphate Ins 1 4 5 P 3 a calcium


id: cord-022888-dnsdg04n
type: GO
entity:
  microbial species Streptococcus pneumoniae Branhamella catarrhalis Streptococcus pyogenes Haemophilus influenzae Staphylococcus aureus Klebsiella pneumoniae


id: cord-022888-dnsdg04n
type: PRODUCT
entity:
  A D Koepruelue 1 W Ellmeier 1 1 Medical University of Vienna Institute of Immunology Division of Immunobiology


id: cord-022888-dnsdg04n
type: ORG
entity:
  LIMES Institute Laboratory for Genomics and Immunoregulation University of Bonn Bonn Germany 2 Institute of Molecular Medicine and


id: cord-022888-dnsdg04n
type: FAC
entity:
  H P Prakash 1 2 1 German Cancer Research Centre Translational Immunology Heidelberg Germany 2 Max Planck Institute for Infection


id: cord-022888-dnsdg04n
type: MONEY
entity:
  between CD45 and CD148 in human T cells not appreciated so far During the past decades great efforts have been made to get insights into the complex process of antigen induced T cell activation and


id: cord-022888-dnsdg04n
type: FAC
entity:
  P Németh 1 T Berki 1 1 University of Pécs Clinical Center Department of Immunology and Biotechnology Pécs Hungary 2


id: cord-022888-dnsdg04n
type: ORG
entity:
  Copenhagen University Institute of International Health Immunology and Microbiology Department of Experimental Immunology


id: cord-022888-dnsdg04n
type: ORG
entity:
  University of Illinois at Chicago Microbiology and Immunology Chicago United StatesObjectives Adenoviruses Ads


id: cord-022888-dnsdg04n
type: ORG
entity:
  University of Vigo Area of Immunology Department of Biochemistry Genetics and Immunology Vigo Spain 2 University of Santiago de Compostela Nanobiofar Group Department of Pharmacy and Pharmaceutical Technology


id: cord-022888-dnsdg04n
type: DISEASE
entity:
  bone marrow and spleen to the site of restimulation e g the peritoneum and the draining lymph nodes Peripheral blood basophils


id: cord-022888-dnsdg04n
type: CHEMICAL
entity:
  G N Drannik 1 T V Poroshina 1 1 Institut of Urology AMSci of Ukraine Laboratory Immunology Kyiv Ukraine


id: cord-022888-dnsdg04n
type: DISEASE
entity:
  HIV and HC p 0 017 and p 0 019 respectively and consequently a lower G allele frequency p 0 026 and p 0 028 respectively No significant differences were found for the 667 SNP


id: cord-022888-dnsdg04n
type: CHEMICAL
entity:
  N Manoussakis 1 1 University of Athens Dpt Pathophysiology Athens Greece 2 University of Erlangen Numberg Institute for Clinical Immunology Erlangen Numberg Germany Objectives Altered phagocytic capacity


id: cord-022888-dnsdg04n
type: CHEMICAL
entity:
  Durilova 1 T Ulmannova 1 K Stechova 1 K Tesarova Flajsmanova 1 V Stavikova 1 J Nevoral 1 1 Charles University Pediatrics Prague Czech


# bib

id: cord-000149-dp8971im
title: Definition of Mafa-A and -B haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis)
author: Otting, Nel
date: 2009-11-24
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802488/
doi: 10.1007/s00251-009-0412-9
abstract:
  The major histocompatibility complex (MHC) class I B gene/allelic repertoire was investigated in a pedigreed population of cynomolgus macaques of mixed Indonesian/Malaysian origin. The Mafa-B alleles detected in this cohort are mostly specific for a given geographic area, and only a small number of alleles appears to be shared with other populations. This suggests the fast evolution of Mafa-B alleles due to adaptation to new environments. In contrast to humans, the B locus in Old World monkeys displays extensive copy number variation. The Mafa-B and previously defined -A gene combinations segregate in families and thus allowed the definition of extended haplotypes. In many cases it was possible to assign a particular Mafa-I allele to one of these Mafa-A/B haplotypes as well. The presence of a large number of stable haplotypes in this cohort of animals, which was pedigreed for up to eight generations, looks promising for developing discriminative MHC typing tools that are less cumbersome. Furthermore, the discovery of 53 unreported Mafa-B sequences expands the lexicon of alleles significantly, and may help in understanding the complex organisation of the macaque B region.


id: cord-000224-2lz03oqb
title: Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag
author: Porter, Kristen A.
date: 2010-06-24
txt: ./txt/cord-000224-2lz03oqb.txt
cache: ./cache/cord-000224-2lz03oqb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892040/
doi: 10.1371/journal.pone.0011304
summary:
  METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. We hypothesized that recapitulating endogenous expression of the entire class II antigen presentation pathway in producer cells via expression of CIITA would restore infectious virus release and provide a more physiologically relevant model for HIV-1 assembly studies. Virus release, both infectious and particle titers) were reduced when cells were transfected with either HLA-DR or other components of the MHC class II antigen presentation pathway ( Figure S2 ), confirming a correlation between Gag retention and reduced virus titers in the presence of HLA-DR, as previously demonstrated [8] . Together, these data suggest CIITA has two effects on the HIV replicative cycle in producer cells, both of which are independent of the MHC II antigen processing pathway; i) it does not induce HLA-DR, mediated intracellular retention of Gag and ii) it increases the infectivity of HIV virions.

abstract:
  BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.


id: cord-000479-u87eaaj8
title: Protein Disulfide Isomerase and Host-Pathogen Interaction
author: Stolf, Beatriz S.
date: 2011-10-11
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201685/
doi: 10.1100/2011/289182
abstract:
  Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections.


id: cord-000488-x5ardo5j
author: Pedersen, Lasse Eggers
date: 2011-07-08
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214623/
doi: 10.1007/s00251-011-0555-3
title:
  Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

abstract:
  In all vertebrate animals, CD8(+) cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC effectively individualizes the immune response of each member of the species. We have recently developed efficient methods to generate recombinant human MHC-I (also known as human leukocyte antigen class I, HLA-I) molecules, accompanying peptide-binding assays and predictors, and HLA tetramers for specific CTL staining and manipulation. This has enabled a complete mapping of all HLA-I specificities (“the Human MHC Project”). Here, we demonstrate that these approaches can be applied to other species. We systematically transferred domains of the frequently expressed swine MHC-I molecule, SLA-1*0401, onto a HLA-I molecule (HLA-A*11:01), thereby generating recombinant human/swine chimeric MHC-I molecules as well as the intact SLA-1*0401 molecule. Biochemical peptide-binding assays and positional scanning combinatorial peptide libraries were used to analyze the peptide-binding motifs of these molecules. A pan-specific predictor of peptide–MHC-I binding, NetMHCpan, which was originally developed to cover the binding specificities of all known HLA-I molecules, was successfully used to predict the specificities of the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules. These data indicate that it is possible to extend the biochemical and bioinformatics tools of the Human MHC Project to other vertebrate species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-011-0555-3) contains supplementary material, which is available to authorized users.


id: cord-000695-g5sum116
author: Hou, Yanxia
date: 2012-06-20
txt: ./txt/cord-000695-g5sum116.txt
cache: ./cache/cord-000695-g5sum116.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3379973/
doi: 10.1371/journal.pone.0039344
summary:
  For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. The NP protein sequence of H5N1 isolate A/Goose/Gongdong/1/96 (H5N1) was downloaded from the UniProt database (UniProtID: NCAP_I96A0) and automatically parsed as octapep-tides or nonapeptides using a computer program, which was developed in our laboratory, based on the peptide-binding motifs of chicken MHC class I molecules belonging to the B4, B12, B15, and B19 haplotypes [22] . Using a motif combined with a structure-based method, 25 potential T cell epitope peptides were predicted in the H5N1 AIV NP in chickens of B4, B12, B15, and B19 haplotypes. First, this is the first study to determine the structural characteristics of the peptide-binding domains of chicken MHC class I molecules belonging to the B4, B12, B15, and B19 haplotypes using a combined motif-structure method to predict T cell epitopes in chickens.

title:
  Prediction and Identification of T Cell Epitopes in the H5N1 Influenza Virus Nucleoprotein in Chicken

abstract:
  T cell epitopes can be used for the accurate monitoring of avian influenza virus (AIV) immune responses and the rational design of vaccines. No T cell epitopes have been previously identified in the H5N1 AIV virus nucleoprotein (NP) in chickens. For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. H5N1 AIV NP was computationally parsed into octapeptides or nonapeptides according to the peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes. Seventy-five peptide sequences were modelled and their MHC class I molecule-binding abilities were analysed by molecular docking. Twenty-five peptides (Ten for B4, six for B12, two for B15, and seven for B19) were predicted to be potential T cell epitopes in chicken. Nine of these peptides and one unrelated peptide were manually synthesized and their T cell responses were tested in vitro. Spleen lymphocytes were collected from SPF chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and they were stimulated using the synthesized peptides. The secretion of chicken IFN-γ and the proliferation of CD8(+) T cells were tested using an ELISA kit and flow cytometry, respectively. The significant secretion of chicken IFN-γ and proliferation of CD8(+) T lymphocytes increased by 13.7% and 11.9% were monitored in cells stimulated with peptides NP(89–97) and NP(198–206), respectively. The results indicate that peptides NP(89–97) (PKKTGGPIY) and NP(198–206) (KRGINDRNF) are NP T cell epitopes in chicken of certain haplotypes. The method used in this investigation is applicable to predicting T cell epitopes for other antigens in chicken, while this study also extends our understanding of the mechanisms of the immune response to AIV in chicken.


id: cord-000871-ej0e1c4d
author: Kim, Yohan
date: 2013-01-24
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554532/
doi: 10.1371/journal.pcbi.1002884
title:
  Positional Bias of MHC Class I Restricted T-Cell Epitopes in Viral Antigens Is Likely due to a Bias in Conservation

abstract:
  The immune system rapidly responds to intracellular infections by detecting MHC class I restricted T-cell epitopes presented on infected cells. It was originally thought that viral peptides are liberated during constitutive protein turnover, but this conflicts with the observation that viral epitopes are detected within minutes of their synthesis even when their source proteins exhibit half-lives of days. The DRiPs hypothesis proposes that epitopes derive from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products. One potential source of DRiPs is premature translation termination. If this is a major source of DRiPs, this should be reflected in positional bias towards the N-terminus. By contrast, if downstream initiation is a major source of DRiPs, there should be positional bias towards the C-terminus. Here, we systematically assessed positional bias of epitopes in viral antigens, exploiting the large set of data available in the Immune Epitope Database and Analysis Resource. We show a statistically significant degree of positional skewing among epitopes; epitopes from both ends of antigens tend to be under-represented. Centric-skewing correlates with a bias towards class I binding peptides being over-represented in the middle, in parallel with a higher degree of evolutionary conservation.


id: cord-001674-tp4o7fxx
title: Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome
author: Oliveira, Cláudia C.
date: 2015-06-05
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457021/
doi: 10.3389/fimmu.2015.00298
abstract:
  The well described conventional antigen-processing pathway is accountable for most peptides that end up in MHC class I molecules at the cell surface. These peptides experienced liberation by the proteasome and transport by the peptide transporter TAP. However, there are multiple roads that lead to Rome, illustrated by the increasing number of alternative processing pathways that have been reported during last years. Interestingly, TAP-deficient individuals do not succumb to viral infections, suggesting that CD8 T cell immunity is sufficiently supported by alternative TAP-independent processing pathways. To date, a diversity of viral and endogenous TAP-independent peptides have been identified in the grooves of different MHC class I alleles. Some of these peptides are not displayed by normal TAP-positive cells and we therefore called them TEIPP, for “T-cell epitopes associated with impaired peptide processing.” TEIPPs are hidden self-antigens, are derived from normal housekeeping proteins, and are processed via unconventional processing pathways. Per definition, TEIPPs are presented via TAP-independent pathways, but recent data suggest that part of this repertoire still depend on proteasome and metalloprotease activity. An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. The intramembrane cleaving SPP is thereby an important contributor of TAP-independent peptides. Its family members, like the Alzheimer’s related presenilins, might contribute as well, according to our preliminary data. Finally, alternative peptide routing is an emerging field and includes processes like the unfolded protein response, the ER-associated degradation, and autophagy-associated vesicular pathways. These data convince us that there is a world to be discovered in the field of unconventional antigen processing.


id: cord-002463-qhtj1pef
title: In silico-based vaccine design against Ebola virus glycoprotein
author: Dash, Raju
date: 2017-03-21
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367765/
doi: 10.2147/aabc.s115859
abstract:
  Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.


id: cord-002686-zzongyfa
author: Oany, Arafat Rahman
date: 2017-09-07
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610819/
doi: 10.1155/2017/6412353
title:
  Vaccinomics Approach for Designing Potential Peptide Vaccine by Targeting Shigella spp. Serine Protease Autotransporter Subfamily Protein SigA

abstract:
  Shigellosis, a bacillary dysentery, is closely associated with diarrhoea in human and causes infection of 165 million people worldwide per year. Casein-degrading serine protease autotransporter of enterobacteriaceae (SPATE) subfamily protein SigA, an outer membrane protein, exerts both cytopathic and enterotoxic effects especially cytopathic to human epithelial cell type-2 (HEp-2) and is shown to be highly immunogenic. In the present study, we have tried to impose the vaccinomics approach for designing a common peptide vaccine candidate against the immunogenic SigA of Shigella spp. At first, 44 SigA proteins from different variants of S. flexneri, S. dysenteriae, S. boydii, and S. sonnei were assessed to find the most antigenic protein. We retrieved 12 peptides based on the highest score for human leukocyte antigen (HLA) supertypes analysed by NetCTL. Initially, these peptides were assessed for the affinity with MHC class I and class II alleles, and four potential core epitopes VTARAGLGY, FHTVTVNTL, HTTWTLTGY, and IELAGTLTL were selected. From these, FHTVTVNTL and IELAGTLTL peptides were shown to have 100% conservancy. Finally, IELAGTLTL was shown to have the highest population coverage (83.86%) among the whole world population. In vivo study of the proposed epitope might contribute to the development of functional and unique widespread vaccine, which might be an operative alleyway to thwart dysentery from the world.


id: cord-003270-vu9b5a14
author: Panahi, Heidar Ali
date: 2018-10-24
txt: ./txt/cord-003270-vu9b5a14.txt
cache: ./cache/cord-003270-vu9b5a14.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200245/
doi: 10.1371/journal.pone.0205933
summary:
  In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens'' analyses were carried out successively by different tools. For the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and for the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens analyses were considered. In this study, the binding ability of the first step selected peptides to human and mouse MHC molecules, was analyzed by CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock/) server. In cancer immunotherapy, the CTL-mediated responses play the central role in eradication of malignant cells, and the binding of epitopes to MHC-I molecules is an essential step for antigen presentation to CTLs. Thus, in this study, predicted epitopes were primarily selected by their MHC-I binding and processing scores.

title:
  A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

abstract:
  Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues. A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide. Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them. Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response. Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers. Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study. For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes. In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools. Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach. These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers. Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development.


id: cord-003472-ml4pbewf
title: Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations
author: Manczinger, Máté
date: 2019-01-31
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372212/
doi: 10.1371/journal.pbio.3000131
abstract:
  Central players of the adaptive immune system are the groups of proteins encoded in the major histocompatibility complex (MHC), which shape the immune response against pathogens and tolerance to self-peptides. The corresponding genomic region is of particular interest, as it harbors more disease associations than any other region in the human genome, including associations with infectious diseases, autoimmune disorders, cancers, and neuropsychiatric diseases. Certain MHC molecules can bind to a much wider range of epitopes than others, but the functional implication of such an elevated epitope-binding repertoire has remained largely unclear. It has been suggested that by recognizing more peptide segments, such promiscuous MHC molecules promote immune response against a broader range of pathogens. If so, the geographical distribution of MHC promiscuity level should be shaped by pathogen diversity. Three lines of evidence support the hypothesis. First, we found that in pathogen-rich geographical regions, humans are more likely to carry highly promiscuous MHC class II DRB1 alleles. Second, the switch between specialist and generalist antigen presentation has occurred repeatedly and in a rapid manner during human evolution. Third, molecular positions that define promiscuity level of MHC class II molecules are especially diverse and are under positive selection in human populations. Taken together, our work indicates that pathogen load maintains generalist adaptive immune recognition, with implications for medical genetics and epidemiology.


id: cord-004518-jd1wxobz
title: DNA vaccines: are they still just a powerful tool for the future?
author: Běláková, Jana
date: 2007-12-03
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079751/
doi: 10.1007/s00005-007-0044-4
abstract:
  Vaccination is historically one of the most successful strategies for the prevention of infectious diseases. For safety reasons, modern vaccinology tends toward the usage of inactivated or attenuated microorganisms and uses predominantly subunit vaccines. The antigens need to be clearly defined, pure, stable, appropriately composed, and properly presented to the immune system of the host. Differing ratios of various proportions between specific CD4(+) and CD8(+) T cell responses are essential for conferring the required protection in the case of individual vaccines. To stimulate both CD4(+) and CD8(+) T cells, the antigens must be processed and presented to both antigen-presentation pathways, MHC I and MHC II. Protein antigens delivered by vaccination are processed as extracellular antigens. However, extracellularly delivered antigen can be directed towards intracellular presentation pathways in conjugation with molecules involved in antigen cross-presentation, e.g. heat shock proteins, or by genomic-DNA vaccination. In this overview, current knowledge of the host immune response to DNA vaccines is summarized in the introduction. The subsequent sections discuss techniques for enhancing DNA vaccine efficacy, such as DNA delivery to specific tissues, delivery of DNA to the cell cytoplasm or nucleus, and enhancement of the immune response using molecular adjuvants. Finally, the prospects of DNA vaccination and ongoing clinical trials with various DNA vaccines are discussed.


id: cord-004975-4c23d77d
author: Larcher, Clara
date: 1997
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087854/
doi: 10.1007/bf01880670
title:
  Influence of viral infection on expression of cell surface antigens in human retinal pigment epithelial cells

abstract:
  • Background: Subacute viral infection is known to change the phenotype of infected cells, thereby causing immune-mediated tissue damage. The aim of this study was to investigate the expression of different cell surface molecules on human retinal pigment epithelial cells (RPEC) following viral infection, with special emphasis on those having immuneregulatory functions. • Methods: Cultured RPEC were infected with cytomegalovirus (CMV), coxsackievirus B3 (CVB) or herpes simplex virus type I (HSV). Double-staining fluorescence technique was used for visualization of virus infection and cell surface markers in the same cells by laser microscopy. • Results: CMV down-regulated MHC class I antigens on RPEC, whereas CVB and HSV did not alter MHC class I antigen expression. No induction of class 11 antigens was observed in RPEC infected with CVB, HSV or CMV. The intercellular adhesion molecule ICAM-1 (CD54) was strongly expressed in uninfected RPEC, and a slight increase was observed after virus infection. Vascular cell adhesion molecule 1 (VCAM-1) was expressed in low amounts in both uninfected and infected RPEC. No expression of intercellular adhesion molecule 2 (ICAM-2), E-selectin ELAM-1 or lymphocyte-function-associated antigen 1 (LFA-1) was observed on RPEC before or after virus infection. • Conclusion: Down-modulation of immune-regulating cell surface antigens has been suggested to provide a means of long-term survival of viruses in the infected cell, favoring establishment of persistent infection. Our observation in cultured human RPEC indicates that this mechanism might indeed contribute to the development of disease affecting retinal tissue.


id: cord-005330-4k7hc1ww
title: T-cells in human encephalitis
author: Bien, Christian G.
date: 2005
txt: ./txt/cord-005330-4k7hc1ww.txt
cache: ./cache/cord-005330-4k7hc1ww.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090662/
doi: 10.1385/nmm:7:3:243
summary:
  In this review, we attempt to summarize the existing knowledge on T-cell effects and-if availablepotential ways of its therapeutic modification in Rasmussen encephalitis (RE), paraneoplastic encephalomyelitis (PEM), and virus encephalitides. This assumption is based on the neuropathological findings of elements of a cytotoxic T-cell attack within the brains of affected people (Bernal et al., 2002) but also on some other observations regarding anti-Yo, anti-Hu, and anti-Ma syndromes and their respective antigens, cerebellar degenerationrelated protein 2 (cdr2), HuD, and PNMA1. The most prominent evidence for a pathogenetically relevant contribution of T-cells to PEM comes from studies on patients with anti-Yo positive paraneoplastic cerebellar degeneration. study on TCR Vβ families of T-lymphocytes within the brains of anti-Hu positive patients (autopsy specimens) providing evidence for an oligoclonal expansion of CD8 + T-cells are concordant with this concept (Voltz et al., 1998) . Selective expression of Purkinje-cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration Modelling paraneoplastic CNS disease: T-cells specific for the onconeuronal antigen PNMA1 mediate autoimmune encephalomyelitis in the rat

abstract:
  Encephalitis literally means inflammation of the brain. In general, this inflammation can result from a viral or bacterial infection in the brain itself or alternatively from a secondary autoimmune reaction against an infection or a tumor in the rest of the body. Besides this, encephalitis is present in (believed autoimmune) diseases with unknown etiology, such as multiple sclerosis or Rasmussen encephalitis (RE). This article summarizes the existing data on the role of T-cells in the pathogenesis of three types of human encephalitis: RE, paraneoplastic encephalomyelitis, and virus encephalitis. In all of them, T-cells play a major role in disease pathogenesis, mainly mediated by major histocompatiblity complex class I-restricted CD8(+) T-lymphocytes.


id: cord-005393-rhji4io9
title: The effects of interferon-γ on the central nervous system
author: Popko, Brian
date: 1997
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091409/
doi: 10.1007/bf02740619
abstract:
  Interferon-gamma (IFN-γ) is a pleotropic cytokine released by T-lymphocytes and natural killer cells. Normally, these cells do not traverse the blood-brain barrier at appreciable levels and, as such, IFN-γ is generally undetectable within the central nervous system (CNS). Nevertheless, in response to CNS infections, as well as during certain disorders in which the CNS is affected, T-cell traffic across the blood-brain barrier increases considerably, thereby exposing neuronal and glial cells to the potent effects of IFN-γ. A large portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-γ plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical and physiological effects of IFN-γ are discussed in the context of the potential consequences of such activities on the developing and mature nervous systems.


id: cord-005400-50lmj4op
title: Overview of vaccines and vaccination
author: Ada, Gordon
date: 2005
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091467/
doi: 10.1385/mb:29:3:255
abstract:
  Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the kind of the immune responses generated by those vaccines, which are so effective. To date, all licensed vaccines generate especially specific antibodies, which attach to the infectious agent and therefore can very largely prevent infection. These vaccines have been so effective in developed countries in preventing mortality after a subsequent infection that attempts are being made to develop vaccines against many of the remaining infectious agents. Many of the latter are difficult to manipulate; they can cause persisting infections or show great antigenic variation. A range of new approaches to improve selected immune responses, such as immunization with DNA or chimeric live vectors, viral or bacterial, are under intense scrutiny, as well as genomic analysis of the agent.


id: cord-005550-qrrdi667
author: Mayer, F
date: 2007-05-23
txt: ./txt/cord-005550-qrrdi667.txt
cache: ./cache/cord-005550-qrrdi667.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094720/
doi: 10.1038/sj.hdy.6800989
summary:
  title: Non-neutral evolution of the major histocompatibility complex class II gene DRB1 in the sac-winged bat Saccopteryx bilineata Thus, the data are consistent with the hypothesis that recombination gives rise to new alleles at the DRB locus of the sac-winged bat, and these are maintained in the population through balancing selection. We analysed the antigen-binding region of the MHC class II gene DRB of the sac-winged bat Saccopteryx bilineata by sequencing cloned PCR products. In this study, we describe the genetic diversity within exon 2 of the MHC class II gene DRB, and discuss the role of recombination and selection in generating and maintaining high levels of genetic diversity in colonies of the sac-winged bat. Variation at the DRB1 locus; evidence of recombination/ gene conversion Ten alleles were detected within the main sample of 79 individuals from the La Selva population.

title:
  Non-neutral evolution of the major histocompatibility complex class II gene DRB1 in the sac-winged bat Saccopteryx bilineata

abstract:
  The immune genes of the major histocompatibility complex (MHC) are classical examples for high levels of genetic diversity and non-neutral evolution. This is particularly true for the regions containing the antigen-binding sites as, for instance, in the exon 2 of the MHC class II gene DRB. We surveyed, for the first time in the order Chiroptera, the genetic diversity within this exon in the sac-winged bat Saccopteryx bilineata. We detected 11 alleles among 85 bats, of which 79 were sampled in one population. Pairwise comparisons revealed that interallelic sequence differences ranged between 3 and 22%, although nucleotide substitutions were not evenly distributed along the exon sequence. This was most probably the result of intragenic recombination. High levels of sequence divergence and significantly more nonsynonymous than synonymous substitutions (d(N)/d(S)>1) suggest long-term balancing selection. Thus, the data are consistent with the hypothesis that recombination gives rise to new alleles at the DRB locus of the sac-winged bat, and these are maintained in the population through balancing selection. In this respect, the sac-winged bat closely resembles other mammalian species.


id: cord-005953-5z89yeb6
title: Abstracts des 114. Internistenkongresses 2008
author: nan
date: 2008
txt: ./txt/cord-005953-5z89yeb6.txt
cache: ./cache/cord-005953-5z89yeb6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096012/
doi: 10.1007/s00063-008-1026-y
abstract: nan
summary:
  Die anderen beiden Gruppen zeigten zwar in Hinblick auf die Wandstärken einen positiven Effekt, hinsichtlich der Herzfunktion konnten sie jedoch bei bereits deutlich erniedrigten Funktionswerten zum Baseline-Zeitpunkt lediglich stabilisiert werden (Reduktion der Wandstärke nach 3 Jahren ERT: Gruppe wenig Fibrose= 10 mm; Gruppe viel Fibrose= 12 mm) Schlussfolgerung: Die Enzymersatztherapie ist eine effektive Langzeitbehandlung bei Patienten mit Fabry Kardiomyopathie. Der Einfluss der sauren Sphingomyelinase auf die Expression von Matrix-Metalloproteinase-1 in intestinalen Epithelzellen und Fibroblasten Background: The calcineurin (Cn)/NF-AT signaling cascade takes a crucial role during T-cell activation and the development of myocardial hypertrophy. Effective and safe reduction of blood pressue by the combination of amlodipine 5/valsartan 160 mg in patients with hypertension and metabolic risk factors not controlled by amlodipine 5 mg or felodipine 5 mga subanalysis of the express-m trial Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and frequently occurs in patients with coronary heart disease.


id: cord-007275-emmoeuqd
author: Cooper, Joanne C.
date: 2007-08-01
txt: ./txt/cord-007275-emmoeuqd.txt
cache: ./cache/cord-007275-emmoeuqd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110103/
doi: 10.1095/biolreprod.106.057125
summary:
  title: An Impaired Breeding Phenotype in Mice with a Genetic Deletion of Beta-2 Microglobulin and Diminished MHC Class I Expression: Role in Reproductive Fitness(1) Beta-2 microglobulin (B2M) plays a pivotal role in the biology of mammals, including its association with major histocompatibility complex (MHC) Class I gene products. Here we report the results of a longitudinal study of the reproductive performance of a genetically modified B2m deficient mouse strain with low MHC Class I expression. In the course of experiments designed to generate mouse embryos for gene transcription studies and immuno-detection of MHC products [50] [51] , we consistently observed an impaired reproductive capacity in the B2m deficient mice. Therefore, a possible mechanism operating in the B2m-deficient mice is the absence of secreted MHC class I products, and thus the absence of mating signals resulting in impaired breeding.

title:
  An Impaired Breeding Phenotype in Mice with a Genetic Deletion of Beta-2 Microglobulin and Diminished MHC Class I Expression: Role in Reproductive Fitness(1)

abstract:
  Beta-2 microglobulin (B2M) plays a pivotal role in the biology of mammals, including its association with major histocompatibility complex (MHC) Class I gene products. The latter molecules have been shown to affect reproduction in both mice and humans, although the exact mechanism is still unknown. Here we report the results of a longitudinal study of the reproductive performance of a genetically modified B2m deficient mouse strain with low MHC Class I expression. Our data show that this mouse strain has an impaired reproductive performance. However, the mice superovulate well and show a normal estrous cycle. Breeding studies from crosses between the transgenic mice and the wild-type parental strain show that B2m deficient mice have a significantly lower frequency of mating than the control B2m(+/+) mice. In addition, the litter size and weaning success of B2m deficient mice were lower than the control. Perinatal lethality of the B2m deficient offspring was also inflicted by cannibalism of the young pups by the B2m deficient female. The impaired breeding phenotype (IBP) can be reversed by reintroducing the B2m gene in F1 heterozygous B2m(+/−) animals; thus the presence of B2M confers a normal breeding pattern. The acquisition of an impaired breeding phenotype (IBP) as a result of the knockout of B2m directly implicates B2M in the reproductive cycle of mice and raises the possibility of an effect of B2M on the reproduction of other mammals.


id: cord-007301-5m269nzi
title: Modeling the adaptive immune system: predictions and simulations
author: Lundegaard, Claus
date: 2007-12-15
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110254/
doi: 10.1093/bioinformatics/btm471
abstract:
  Motivation: Immunological bioinformatics methods are applicable to a broad range of scientific areas. The specifics of how and where they might be implemented have recently been reviewed in the literature. However, the background and concerns for selecting between the different available methods have so far not been adequately covered. Summary: Before using predictions systems, it is necessary to not only understand how the methods are constructed but also their strength and limitations. The prediction systems in humoral epitope discovery are still in their infancy, but have reached a reasonable level of predictive strength. In cellular immunology, MHC class I binding predictions are now very strong and cover most of the known HLA specificities. These systems work well for epitope discovery, and predictions of the MHC class I pathway have been further improved by integration with state-of-the-art prediction tools for proteasomal cleavage and TAP binding. By comparison, class II MHC binding predictions have not developed to a comparable accuracy level, but new tools have emerged that deliver significantly improved predictions not only in terms of accuracy, but also in MHC specificity coverage. Simulation systems and mathematical modeling are also now beginning to reach a level where these methods will be able to answer more complex immunological questions. Contact: lunde@cbs.dtu.dk Supplementary information: Supplementary data are available at Bioinformatics online.


id: cord-007603-27m9wz0i
author: Rall, Glenn F.
date: 2002-11-11
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119529/
doi: 10.1016/0165-5728(94)90163-5
title:
  A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes

abstract:
  Astrocytes provide crucial support for neurons and their impairment by viruses or their interactions with anti-viral or autoimmune responses could contribute to neurological disease. We have developed a transgenic mouse model to assess lymphocyte-astrocyte interactions. The major histocompatibility complex (MHC) class I molecule, D(b), was expressed in astrocytes under the transcriptional control of regulatory sequences from the glial fibrillary acidic protein (GFAP) gene. Baseline cerebral MHC class I mRNA levels from transgenic mice were elevated over those of non-transgenic controls, and a prominent increase in cerebral MHC class I expression occurred following focal, injury-induced astroglial activation within transgenic brains but not in non-transgenic controls. FACS analysis of explant astrocyte cultures from established transgenic lines demonstrated astroglial expression of the GFAP-D(b) fusion gene at the protein level. Functional antigen-presenting capacity was conferred by the D(b) transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (K(d)I(d)D(d)L(d)) expressing the D(b) molecule were lysed by D(b)-restricted anti-viral CTL.


id: cord-007621-rapinodd
author: Vidovic, Maria
date: 2002-11-13
txt: ./txt/cord-007621-rapinodd.txt
cache: ./cache/cord-007621-rapinodd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119667/
doi: 10.1016/0165-5728(90)90103-t
summary:
  Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. To determine the steady-state level of mRNA for class II, Northern blot analysis was performed using a eDNA probe for murine class Ii genes (E-a), with total RNA isolated from cultured astrocytes. The duration of protein synthesis required to allow expression of the class II MHC gene in astrocytes was examined in cells that were pretreated with IFN-y or IFN-7/TNF-a for different lengths of time prior to the addition of CHX. In this study we have shown that primary neonatal rat astrocytes, upon stimulation with IFN-~,, express mRNA transcripts for class II MHC genes, and that TNF-a enhances the expression of IFN-~,-induced class II mRNA. The expression of class II mRNA was completely inhibited when CHX was included with IFN-~, and IFN-''t/TNF-~ treatment, indicating that newly synthesized protein is required for astrocyte class II MHC gene expression.

title:
  Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-γ and tumor necrosis factor-α

abstract:
  Astrocytes can function as antigen-presenting cells (APC) upon expression of class II major histocompatibility complex (MHC) antigens, which are induced by interferon-γ (IFN-γ). Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. We have now investigated the effect of IFN-γ and TNF-α on class II MHC mRNA expression in astrocytes using Northern blot analysis. Astrocytes do not constitutively express mRNA for class II MHC. Kinetic analysis of class II MHC mRNA expression in IFN-γ-treated cells demonstrated an 8 h time lag, which was followed by an increase over the next 16 h. Optimal expression of class II mRNA was detected after a 24 h incubation with IFN-γ. This level of expression was further enhanced by the simultaneous addition of IFN-γ and TNF-α to the astrocytes, while TNF-α alone had no effect on class II mRNA expression. TNF-α does not act by increasing the stability of IFN-γ-induced class II mRNA, indicating its action is not at that specific level of post-transcriptional control. Furthermore, astrocyte class II mRNA expression was inhibited when cycloheximide (CHX) was added together with IFN-γ or IFN-γ/TNF-α, and when CHX was added up to 4 h after treatment with IFN-γ or IFN-γ/TNF-α. These results indicate that astrocyte class II mRNA expression is mediated by newly synthesized proteins induced by IFN-γ and/or IFN-γ/TNF-α. The expression of class II antigens on astrocytes, and cytokine modulation of their expression, may be important in the initiation and perpetuation of intracerebral immune responses.


id: cord-007636-kfd0wqdx
author: Wen, P.
date: 2002-11-13
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119745/
doi: 10.1016/0165-5728(90)90074-w
title:
  The effects of irradiation on major histocampatibility complex expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model

abstract:
  The effects of irradiation on major histocompatibility complex (MHC) expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model were examined. Doses of irradiation administered were biologically equivalent to that used in the treatment of patients with malignant gliomas. No significant change in immune parameters was observed following irradiation in the normal rat brain. In the 9L gliosarcoma model irradiation did not suppress MHC expression or lymphocytic infiltration. These findings suggest that prior exposure to therapeutic irradiation need not adversely affect subsequent immunotherapies, and provide a foundation for future studies of immunomodulation in the irradiated brain.


id: cord-007654-lchdm4xr
author: Liu, Yang
date: 2002-12-11
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119853/
doi: 10.1016/0165-5728(89)90171-9
title:
  Flavivirus infection up-regulates the expression of class I and class II major histocompatibility antigens on and enhances T cell recognition of astrocytes in vitro

abstract:
  West Nile virus (WNV) infection of astrocytes can up-regulate their expression of both class I and class II major histocompatibility complex (MHC) antigens as determined by flow cytometry with monoclonal antibodies specific for class I and class II MHC antigens. The up-regulation of class I MHC antigen expression could be partly caused by interferon secreted after WNV infection because the synthetic interferon inducer polyinosinic-polycytidylic acid (poly I : C) has similar effects. In contrast the up-regulation of class II MHC antigen expression was not induced by poly I : C. The increased MHC antigen expression by WNV infection had significant effects on T cell recognition. Thus, WNV and influenza virus A/WSN double-infected astrocytes but not astrocytes infected by A/WSN alone were lysed by influenza virus-immune cytotoxic T cells. Similarly, WNV-infected astrocytes were better stimulators than normal astrocytes for a class II MHC-reactive T cell line, both in terms of T cell proliferation and interleukin release.


id: cord-007851-v6h1yro7
author: Han, Ki-Cheol
date: 2020-04-03
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125174/
doi: 10.1038/s41598-020-62244-z
title:
  Streamlined selection of cancer antigens for vaccine development through integrative multi-omics and high-content cell imaging

abstract:
  Identification of tumor antigens that induce cytotoxic T lymphocytes (CTLs) is crucial for cancer-vaccine development. Despite their predictive ability, current algorithmic approaches and human leukocyte antigen (HLA)-peptidomic analysis allow limited selectivity. Here, we optimized a method to rapidly screen and identify highly immunogenic epitopes that trigger CTL responses. We used a combined application of this method involving immune-specific signature analysis and HLA-associated peptidomics using samples from six patients with triple-negative breast cancer (TNBC) in order to select immunogenic HLA epitopes for in vitro testing. Additionally, we applied high-throughput imaging at the single-cell level in order to confirm the immunoreactivity of the selected peptides. The results indicated that this method enabled identification of promising CTL peptides capable of inducing antitumor immunity. This platform combining high-resolution computational analysis, HLA-peptidomics, and high-throughput immunogenicity testing allowed rapid and robust identification of highly immunogenic epitopes and represents a powerful technique for cancer-vaccine development.


id: cord-008523-avkgldnp
title: Selection of and evasion from cytotoxic T cell responses in the central nervous system
author: Perlman, Stanley
date: 2004-01-07
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131566/
doi: 10.1016/s0065-3527(01)56029-7
abstract:
  Cytotoxic CD8 T lymphocytes (CTLs) are critical for the clearance of noncytopathic viruses from infected cells. This chapter discusses one mechanism used by viruses to persist—namely, the selection of a variant virus in which changes in the sequence of a CTL epitope abrogate recognition. The unique features of cytotoxic CD8 T cell function in the central nervous system (CNS) are discussed. The role of CTL escape mutants in the viral evasion of the immune system and subsequent disease progression in non-CNS infections are summarized. The immune response in the CNS is similar to the response in extraneural tissue, but several aspects of the activation of the immune response, cellular trafficking, and antigen presentation are unique to the CNS. Although the CNS has classically been considered a site of immune privilege, surveillance of the normal CNS by circulating, activated lymphocytes occurs, with a limited number of lymphocytes being present in the normal CNS at any given time. In mice infected with mouse hepatitis virus and in some humans persistently infected with human immunodeficiency virus type1, hepatitis B virus or hepatitis C virus, CTL escape mutants play an important role in virus amplification and disease progression.


id: cord-009567-osstpum6
title: Abstracts Oral
author: nan
date: 2008-04-23
txt: ./txt/cord-009567-osstpum6.txt
cache: ./cache/cord-009567-osstpum6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159651/
doi: 10.1111/j.1600-6143.2008.02254.x
abstract: nan
summary:
  Introduction: Previously, it has been demonstrated that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during cardiac rejection, suggesting infiltration of regulatory T cells in the transplanted organ during an allogeneic response. Efficacy and safety parameters assessed at follow-up included: acute rejection; patient and graft survival; renal function, vital signs, basic lab results and immunosuppressive regimen for the patients 10 years after completion of the original study. We analyzed, for the first time, the expression of TLR4 in PBMC from kidney recipients with contrasted situations: operational tolerance and chronic immune-mediated rejection (Banff 2005), compared to patients with normal histology and stable graft function, non transplant patients with renal failure and healthy volunteers.


id: cord-009570-djxoiytq
author: Gran, Bruno
date: 2001-06-01
txt: ./txt/cord-009570-djxoiytq.txt
cache: ./cache/cord-009570-djxoiytq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159663/
doi: 10.1002/1531-8249(199905)45:5<559::aid-ana3>3.0.co;2-q
summary:
  Both clinical and experimental evidence supports the hypothesis that immune mechanisms are involved in the pathogenesis of inflammatory demyelination in multiple sclerosis (MS) and that autoreactive T lymphocytes initiate the process of central nervous system (CNS) myelin damage. This disease model has provided insight into the pathogenic "steps" that may be relevant to MS, including (1) genetic susceptibility, (2) priming and activation of myelin-specific T cells, (3) interaction of autoreactive T cells with endothelium and migration into the CNS, and (4) recognition of myelin antigens and initiation of inflammatory or demyelinating damage (Fig 1) . 44, 45 Molecular mimicry motifs that would satisfy both MHC binding and recognition by specific TCR were used by Wucherpfennig and Strominger 46 to identify microbial peptides that were effective in activating three MBPspecific T-cell clones (TCCs) derived from MS patients (Table 1) . Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein

title:
  Molecular mimicry and multiple sclerosis: Degenerate T‐cell recognition and the induction of autoimmunity

abstract:
  Various mechanisms have been proposed for the initiation of autoimmune responses by autoreactive T‐cell clones. One of these, the molecular mimicry hypothesis, postulates that myelin‐reactive T‐cell clones are activated by foreign antigens. Until recently, sequence homology between self‐ and foreign antigens was considered necessary for cross‐recognition to occur in multiple sclerosis. This article reviews current progress in T‐cell receptor immunology that led to modify this view and proposes a role for degenerate T‐cell antigen recognition in the induction of autoimmunity. Ann Neurol 1999;45:559–567


id: cord-010500-ajmj2hyj
title: Limited polymorphism at major histocompatibility complex (MHC) loci in the Swedish moose A. alces
author: ELLEGREN, H.
date: 2008-06-28
txt: ./txt/cord-010500-ajmj2hyj.txt
cache: ./cache/cord-010500-ajmj2hyj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192233/
doi: 10.1111/j.1365-294x.1996.tb00286.x
summary:
  The Swedish moose was analysed for genetic variability at major histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) techniques. Since the SSCP analysis concerned an expressed DRB gene it can be concluded that the level of functional MHC class II polymorphism, at least at the DRB locus, is low in Swedish moose. As an illustration of the varying levels of MHC polymorphism in cattle and moose, a blot with bovine PVuII digests hybridized with the same human DQB probe as employed in the present study is shown in Fig. I@) . There is a clear difference between the moose and cattle as regards their degrees of MHC polymorphism in relation to their genome-wide genetic variability measured by DNA fingerprinting.

abstract:
  The Swedish moose was analysed for genetic variability at major histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) techniques. Both methods revealed limited amounts of polymorphism. Since the SSCP analysis concerned an expressed DRB gene it can be concluded that the level of functional MHC class II polymorphism, at least at the DRB locus, is low in Swedish moose. DNA fingerprinting was used to determine if the unusual pattern of low MHC variability could be explained by a low degree of genome‐wide genetic diversity. Hybridizations with two minisatellite probes gave similarity indices somewhat higher than the average for other natural population, but the data suggest that the low MHC variability cannot be explained by a recent population bottleneck. However, since minisatellite sequences evolve more rapidly than MHC sequences, the low levels of MHC diversity may be attributed to a bottleneck of more ancient origin. The selection pressure for MHC variability in moose may also be reduced and we discuss the possibility that its solitary life style may reduce lateral transmission of pathogens in the population.


id: cord-010508-jtbxefm4
author: Mohammed, Arwa A.
date: 2020-04-22
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193299/
doi: 10.1155/2020/2567957
title:
  Epitope-Based Peptide Vaccine against Glycoprotein G of Nipah Henipavirus Using Immunoinformatics Approaches

abstract:
  BACKGROUND: Nipah belongs to the genus Henipavirus and the Paramyxoviridae family. It is an endemic most commonly found at South Asia and has first emerged in Malaysia in 1998. Bats are found to be the main reservoir for this virus, causing disease in both humans and animals. The last outbreak has occurred in May 2018 in Kerala. It is characterized by high pathogenicity and fatality rates which varies from 40% to 70% depending on the severity of the disease and on the availability of adequate healthcare facilities. Currently, there are no antiviral drugs available for NiV disease and the treatment is just supportive. Clinical presentations for this virus range from asymptomatic infection to fatal encephalitis. OBJECTIVE: This study is aimed at predicting an effective epitope-based vaccine against glycoprotein G of Nipah henipavirus, using immunoinformatics approaches. METHODS AND MATERIALS: Glycoprotein G of the Nipah virus sequence was retrieved from NCBI. Different prediction tools were used to analyze the epitopes, namely, BepiPred-2.0: Sequential B Cell Epitope Predictor for B cell and T cell MHC classes II and I. Then, the proposed peptides were docked using Autodock 4.0 software program. Results and Conclusions. The two peptides TVYHCSAVY and FLIDRINWI have showed a very strong binding affinity to MHC class I and MHC class II alleles. Furthermore, considering the conservancy, the affinity, and the population coverage, the peptide FLIDRINWIT is highly suitable to be utilized to formulate a new vaccine against glycoprotein G of Nipah henipavirus. An in vivo study for the proposed peptides is also highly recommended.


id: cord-010640-s1oqphvn
author: Baral, Prabin
date: 2020-05-06
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203123/
doi: 10.1038/s41598-020-63640-1
title:
  In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever

abstract:
  Lassa virus (LASV), a member of the Arenaviridae, is an ambisense RNA virus that causes severe hemorrhagic fever with a high fatality rate in humans in West and Central Africa. Currently, no FDA approved drugs or vaccines are available for the treatment of LASV fever. The LASV glycoprotein complex (GP) is a promising target for vaccine or drug development. It is situated on the virion envelope and plays key roles in LASV growth, cell tropism, host range, and pathogenicity. In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In addition, many sequence- and structure-based computational prediction tools were used to identify LASV GP B-cell epitopes. The predicted T- and B-cell epitopes were further filtered based on the consensus approach that resulted in the identification of thirty new epitopes that have not been previously tested experimentally. Epitope-allele complexes were obtained for selected strongly binding alleles to the MHC-I T-cell epitopes using molecular docking and the complexes were relaxed with molecular dynamics simulations to investigate the interaction and dynamics of the epitope-allele complexes. These predictions provide guidance to the experimental investigations and validation of the epitopes with the potential for stimulating T-cell responses and B-cell antibodies against LASV and allow the design and development of LASV vaccines.


id: cord-011173-c1i0a92f
title: Improved MHC II epitope prediction — a step towards personalized medicine
author: Moore, Tamson V.
date: 2019-12-13
txt: ./txt/cord-011173-c1i0a92f.txt
cache: ./cache/cord-011173-c1i0a92f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223749/
doi: 10.1038/s41571-019-0315-0
summary:
  Whereas the presence and expression of neoantigen proteins can be identified through sequencing of the tumour exome, the neoepitopes presented by MHC II molecules must be either discovered empirically using expensive and time-consuming mass spectrometry (MS) techniques 4 or predicted using software-based estimations of peptide-MHC II binding affinity. The deconvoluted peptidomic datasets were then used to train a prediction algorithm, MixMHC2pred, which returns an MHC II binding score for a given peptide sequence and HLA-D allele. The efficacy of such neoantigen-based immunotherapies will be dependent on the identification of a sufficient number of MHC II-binding peptides to stimulate CD4 + T cell responses. Both MARIA and MixMHC2pred have the potential to make personalized neoantigen-based therapies more accessible to patients, including patients with tumours harbouring fewer mutations, by identifying more MHC II-binding epitopes to which CD4 + T cells can respond within each patient''s pool of putative neoantigens.

abstract:
  Numerous neoepitope-based vaccination strategies are in testing for clinical use in the treatment of cancer. Rapid identification of immunostimulatory neoantigen targets hastens neoantigen vaccine development. Papers recently published in Nature Biotechnology describe two independent machine-learning-based algorithms that demonstrate improved identification of MHC class II-binding peptides. Herein, we outline the benefits of these algorithms and their implications for future immunotherapies.


id: cord-013093-aa4cf44u
title: Deciphering and predicting CD4(+) T cell immunodominance of influenza virus hemagglutinin
author: Cassotta, Antonino
date: 2020-07-09
txt: ./txt/cord-013093-aa4cf44u.txt
cache: ./cache/cord-013093-aa4cf44u.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537397/
doi: 10.1084/jem.20200206
summary:
  The detailed and unbiased characterization of HA-reactive memory and naive CD4 + T cell repertoires, paralleled by a deep analysis of the naturally presented repertoire of MHC-II-binding HA peptides by mass spectrometry (MS)-based immunopeptidomics, allowed us to shed new light on the factors governing CD4 + T cell clonal selection and immunodominance to influenza HA in humans. We then selected a large number of H1-HA-specific T cell clones derived from naive or memory T cells of donor HD1 and determined their functional avidity by measuring the proliferative response to autologous monocytes pulsed with different concentrations of the H1-HA peptides or H1-HA protein, which need processing for presentation on MHC-II molecules.

abstract:
  The importance of CD4(+) T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4(+) T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4(+) T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry–based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.


id: cord-013315-plptulfb
author: Tilocca, Bruno
date: 2020-08-27
txt: ./txt/cord-013315-plptulfb.txt
cache: ./cache/cord-013315-plptulfb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558617/
doi: 10.3390/pathogens9090705
summary:
  The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The class I MHC epitopes as of Figure 3 are further aligned against both the mycobacteria and cow databases to assess the specificity of the predicted epitope sequences for MAP. To prove selected epitopes as suitable candidates for the unbiased diagnosis of MAP infection, we aligned the peptides sequences against a database comprising the closest taxonomically-related bacteria. Selected peptide sequences of the immunoreactive proteins were searched against the NCBInr database restricted to Mycobacterium avium subsp. Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome

title:
  Immunoinformatic-Based Prediction of Candidate Epitopes for the Diagnosis and Control of Paratuberculosis (Johne’s Disease)

abstract:
  Paratuberculosis is an infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is an intracellular pathogen with a possible zoonotic potential since it has been successfully isolated from the intestine and blood of Crohn’s disease patients.Since no cure is available, after the detection of the disease, animal culling is the sole applicable containment strategy. However, the difficult detection of the disease in its subclinical form, facilitates its spread raising the need for the development of effective diagnosis and vaccination strategies. The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. These proteins were chosen according to a previously published immunoproteomics approach. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The retrieved peptide sequences were analyzed for their specificity and cross-reactivity. The final aim is to employ the discovered peptides sequences as a filtered library useful for early-stage diagnosis and/or to be used in novel multi-subunit or recombinant vaccine formulations.


id: cord-013590-pkm81fq1
title: Ligand recognition by the γδ TCR and discrimination between homeostasis and stress conditions
author: Deseke, Malte
date: 2020-07-24
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608190/
doi: 10.1038/s41423-020-0503-y
abstract:
  T lymphocytes comprise cells expressing either an αβ or a γδ TCR. The riddle how αβ TCRs are triggered by specific peptides presented in the context of MHC was elucidated some time ago. In contrast, the mechanisms that underlie antigen recognition by γδ TCRs are still baffling the scientific community. It is clear that activation of γδ TCRs does not necessarily depend on MHC antigen presentation. To date, diverse and largely host-cell-derived molecules have been identified as cognate antigens for the γδ TCR. However, for most γδ TCRs, the activating ligand is still unknown and many open questions with regard to physiological relevance and generalizable concepts remain. Especially the question of how γδ T cells can distinguish homeostatic from stress conditions via their TCR remains largely unresolved. Recent discoveries in the field might have paved the way towards a better understanding of antigen recognition by the γδ TCR and have made it conceivable to revise the current knowledge and contextualize the new findings.


id: cord-016594-lj0us1dq
title: Identification of Candidate Vaccine Antigens In Silico
author: Flower, Darren R.
date: 2012-09-28
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120937/
doi: 10.1007/978-1-4614-5070-2_3
abstract:
  The identification of immunogenic whole-protein antigens is fundamental to the successful discovery of candidate subunit vaccines and their rapid, effective, and efficient transformation into clinically useful, commercially successful vaccine formulations. In the wider context of the experimental discovery of vaccine antigens, with particular reference to reverse vaccinology, this chapter adumbrates the principal computational approaches currently deployed in the hunt for novel antigens: genome-level prediction of antigens, antigen identification through the use of protein sequence alignment-based approaches, antigen detection through the use of subcellular location prediction, and the use of alignment-independent approaches to antigen discovery. Reference is also made to the recent emergence of various expert systems for protein antigen identification.


id: cord-017629-fuv157f1
title: Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety
author: De Groot, Anne S.
date: 2008-07-31
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122239/
doi: 10.1007/978-0-387-79208-8_3
abstract:
  Vaccine science has extended beyond genomics to proteomics and has come to also encompass ‘immunomics,’ the study of the universe of pathogen-derived or neoplasm-derived peptides that interface with B and T cells of the host immune system. It has been theorized that effective vaccines can be developed using the minimum essential subset of T cell and B cell epitopes that comprise the ‘immunome.’ Researchers are therefore using bioinformatics sequence analysis tools, epitope-mapping tools, microarrays, and high-throughput immunology assays to discover the minimal essential components of the immunome. When these minimal components, or epitopes, are packaged with adjuvants in an appropriate delivery vehicle, the complete package comprises an epitope-based immunome-derived vaccine. Such vaccines may have a significant advantage over conventional vaccines, as the careful selection of the components may diminish undesired side effects such as have been observed with whole pathogen and protein subunit vaccines. This chapter will review the pre-clinical and anticipated clinical development of computer-driven vaccine design and the validation of epitope-based immunome-derived vaccines in animal models; it will also include an overview of heterologous immunity and other emerging issues that will need to be addressed by vaccines of all types in the future.


id: cord-017819-85x0juiw
title: Biological conservation and parasitism
author: Christe, Philippe
date: 2006
txt: ./txt/cord-017819-85x0juiw.txt
cache: ./cache/cord-017819-85x0juiw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122491/
doi: 10.1007/978-4-431-36025-4_27
abstract: nan
summary:
  It is, therefore, not surprising that corticosteroid level is measured in many studies in ecology and conservation biology that have evaluated the effect of different environmental and human perturbations on the stress level of wild animals (Creel et al. In contrast, widespread host species that live in high density are exposed to a wide range of parasite species that may affect drastically the population dynamics of these carnivores, suggesting that macroparasites may regulate them at least locally. Interestingly, Allee effects and parasitism have several features in common that are of interest when studying population dynamics in conservation biology (Deredec 2005) . Invasive host species have another advantage if they have invested in strong immune defences in their natural range, which may then subsequently confer a better capacity to control parasites that they may acquire in the introduced habitat.


id: cord-018034-gx5c9mk8
title: Cell and Tissue Reactions
author: nan
date: 2006
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122794/
doi: 10.1007/3-540-28995-x_4
abstract:
  Similar types of tissue reaction result as a final common pathway from a wide array of different internal brain pathophysiological states and external insults. Since these cellular and tissue reactions are largely independent of the specific type of insults, they are, therefore, non-specific. The tissue reactions are to be differentiated according to their specific pathogenetic mechanisms, though these mechanisms as well as the phenomena are overlapping as demonstrated in Fig. 4.1; brain ischemia as a type of metabolic disturbance, edema, intracranial pressure, necrosis, herniation and inflammation are influencing themselves and are dependent on each other. Some will be mentioned again in later chapters as viewed from different forensic aspects; therefore, a certain redundancy is unavoidable. Immediately following, we offer a survey of the individual types of reaction and their fundamental pathophysiological principles and morphology.


id: cord-021079-m6nbs2c0
title: Major histocompatibility complex molecules on glial cells
author: Yong, Voon Wee
date: 2004-11-23
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148993/
doi: 10.1016/1044-5765(92)90006-n
abstract:
  While glial cells of the central nervous system do not constitutively express class I or II major histocompatibility complex (MHC) molecules, astrocytes and microglial cells can be induced by a variety of factors to express these antigens. Oligodendrocytes have inducible class I but not class II elements. There are considerable differences in regulation of MHC antigen expression between glial cells from rodent and human brains, both in situ and in vitro. The consequence of glial cell MHC expression for immune interactions in the CNS is discussed in the context of glial cell antigen presentation capacity and neural cell susceptibility to cell-mediated immune effector mechanisms.


id: cord-021693-odfxkfu7
title: Molecular Mimicry in Multiple Sclerosis: Role of MHC-Altered Peptide Ligands (MAPL)
author: Lim, Dong-Gyun
date: 2007-05-09
txt: ./txt/cord-021693-odfxkfu7.txt
cache: ./cache/cord-021693-odfxkfu7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151874/
doi: 10.1016/b978-044451271-0.50004-1
abstract: nan
summary:
  Data from animal studies in the EAE model established that CD4 + Thl cells specific to myelin antigens can play a central role in the induction and progression of autoimmune demyelinating disease [2, 3] . In examining the immune response to MBP, we found that complementary mutations in an antigenic peptide allow for cross-reactivity of autoreacfive T cell clones that may be related to shifts of the TCR structure itself [11] . The new knowledge obtained from this study was 1) that of highly degenerative recognition of peptides by autoreactive CD4 § T cells, including identification of stimulatory ligands not sharing a single amino acid in corresponding positions with the antigen used to establish the T cell clone and 2) the identification of more potent agonistic peptides than cognate self-peptide. Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein Cross-reactive human autoreactive T-ceU receptor responses to altered peptide ligands presented by different MHC class II molecules


id: cord-022142-d4yxgv83
title: Polymer-Based DNA Delivery Systems for Cancer Immunotherapy
author: David, Ayelet
date: 2016-05-28
txt: ./txt/cord-022142-d4yxgv83.txt
cache: ./cache/cord-022142-d4yxgv83.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153417/
doi: 10.1007/978-1-4939-3634-2_10
summary:
  A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter highlights the repertoire of non-viral, nanosized polymeric DNA delivery systems (polyplexes) available to achieve effi cient gene transfer into DCs for immunotherapeutic applications in cancer therapy. With respect to clinical translation, effi cacious non-viral gene delivery into DCs will depend on the combination of intelligent material design, the appropriate tumor specifi c antigen-encoding DNA and immuno-stimulatory molecules to promote DC maturation and activation.

abstract:
  The use of gene delivery systems for the expression of antigenic proteins is an established means for activating a patient’s own immune system against the cancer they carry. Since tumor cells are poor antigen-presenting cells, cross-presentation of tumor antigens by dendritic cells (DCs) is essential for the generation of tumor-specific cytotoxic T-lymphocyte responses. A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter summarizes the physicochemical properties and biological information on polymer-based non-viral vectors used for targeting DCs, and discusses the main challenges for successful in vivo gene transfer into DCs.


id: cord-022395-rk31pwoa
title: Central Nervous System: Viral Infection and Immune-Mediated Inflammation
author: Schuller-Levis, Georgia
date: 2012-12-02
txt: ./txt/cord-022395-rk31pwoa.txt
cache: ./cache/cord-022395-rk31pwoa.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155647/
doi: 10.1016/b978-0-12-628930-5.50019-9
abstract: nan
summary:
  Acute and chronic relapsing EAE can be induced in laboratory animals by an injection of CNS tissue, CNS myelin, myelin basic protein, or more recently, T-cell lines specific for nervous system antigens. Infection with mouse hepatitis virus (MHV), has been shown to block expression of MHC molecules on murine cerebral endothelial cells (see later discussion) (Joseph et al., 1991) . Until recently, the HLA Class I molecules were thought to be the primary, if not the only, HLA recognition structure for CTLs. Studies of measles and Epstein-Barr virus (EBV) infection suggest that HLA Class II molecules can also serve as recognition sites, further expanding the potential action of CTLs. Viral antigens recognized by CTLs have also been expanded beyond the traditional cell surface molecules (Braciale and Braciale, 1986) . The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of virus and lead to CNS disease. Immune response gene products (la antigens) on glial and endothelial cells in virus-induced demyelination


id: cord-022888-dnsdg04n
title: Poster Sessions
author: nan
date: 2009-08-19
txt: ./txt/cord-022888-dnsdg04n.txt
cache: ./cache/cord-022888-dnsdg04n.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/
doi: 10.1002/eji.200990224
abstract: No Abtract
summary:
  Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery.


id: cord-023055-ntbvmssh
title: Immunogenicity
author: nan
date: 2004-02-19
txt: ./txt/cord-023055-ntbvmssh.txt
cache: ./cache/cord-023055-ntbvmssh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166418/
doi: 10.1002/jcb.240410506
abstract: nan
summary:
  Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures.


id: cord-023724-5at0rhqk
title: Infection
author: Cann, Alan J.
date: 2015-07-24
txt: ./txt/cord-023724-5at0rhqk.txt
cache: ./cache/cord-023724-5at0rhqk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173531/
doi: 10.1016/b978-0-12-801946-7.00006-7
summary:
  The problems plant viruses face in initiating infections of host cells have already been described (Chapter 4), as has the fact that no known plant virus employs a specific cellular receptor of the types that animal and bacterial viruses use to attach to cells. There are probably many different mechanisms involved in systemic resistance, but in general terms there is a tendency of these processes to increase local necrosis when substances such as proteases and peroxidases are produced by the plant to destroy the virus and to prevent its spread and subsequent systemic infection. Virus-resistant plants have been created by the production of transgenic plants expressing recombinant virus proteins or nucleic acids which interfere with virus replication without producing the pathogenic consequences of infection, for example: I Virus coat proteins, which have a variety of complex effects, including inhibition of virus uncoating and interference of expression of the virus at the level of RNA ("gene silencing" by "untranslatable" RNAs), I Intact or partial virus replicases which interfere with genome replication, I Antisense RNAs, I Defective virus genomes, I Satellite sequences (see Chapter 8), I Catalytic RNA sequences (ribozymes), I Modified movement proteins.

abstract:
  Virus infection of higher organisms is the cumulative result of all the processes of replication and gene expression described in the previous chapters. Together, these determine the overall course of each infection. Infections range in complexity and duration from a very brief, superficial interaction between the virus and its host to infections that may span the entire life of the host organism, from before birth to its eventual death. A common misconception is that virus infection inevitably results in disease. In reality, the reverse is true—only a small minority of virus infections gives rise to any disease symptoms. This chapter provides an overview of the numerous patterns of virus infection and forms an introduction to the discussion of virus pathogenesis in Chapter 7. Unlike previous and subsequent chapters, this chapter deals primarily with the interaction of viruses with intact organisms rather than with the molecular biologist’s usual concern about the interaction between a virus and the cell.


id: cord-025523-6ttps1nx
title: Cross-Domain Authorship Attribution Using Pre-trained Language Models
author: Barlas, Georgios
date: 2020-05-06
txt: ./txt/cord-025523-6ttps1nx.txt
cache: ./cache/cord-025523-6ttps1nx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256385/
doi: 10.1007/978-3-030-49161-1_22
summary:
  title: Cross-Domain Authorship Attribution Using Pre-trained Language Models An especially challenging but very realistic scenario is cross-domain attribution where texts of known authorship (training set) differ from texts of disputed authorship (test set) in topic or genre. Recently, the use of pre-trained language models (e.g., BERT, ELMo, ULM-FiT, has been demonstrated to obtain significant gains in several text classification tasks including sentiment analysis, emotion classification, and topic classification [2, 7, 13, 14] . This method is based on a character-level recurrent (RNN) neural network language model and a multiheaded classifier (MHC) [1] . We examine the use of pre-trained language models (e.g., BERT, ELMo, ULMFiT, GPT-2) in AA and the potentials of MHC. Based on Bagnall''s model [1] , originally proposed for authorship verification, we compare the performance when we use either the original characterlevel RNN trained from scratch in the small-size AA corpus or pre-trained tokenbased language models obtained from general-domain corpora.

abstract:
  Authorship attribution attempts to identify the authors behind texts and has important applications mainly in cyber-security, digital humanities and social media analytics. An especially challenging but very realistic scenario is cross-domain attribution where texts of known authorship (training set) differ from texts of disputed authorship (test set) in topic or genre. In this paper, we modify a successful authorship verification approach based on a multi-headed neural network language model and combine it with pre-trained language models. Based on experiments on a controlled corpus covering several text genres where topic and genre is specifically controlled, we demonstrate that the proposed approach achieves very promising results. We also demonstrate the crucial effect of the normalization corpus in cross-domain attribution.


id: cord-028945-p3hhd5ed
author: Şahar, Esra Atalay
date: 2020-07-10
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348124/
doi: 10.1186/s12879-020-05220-2
title:
  Development of a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and determination of its protective efficacy against acute toxoplasmosis

abstract:
  BACKGROUND: Toxoplasma gondii is an obligate intracellular parasite that can infect almost all warm-blooded animals, avian species and humans. Toxoplasmosis is asymptomatic in healthy individuals, whereas it may lead to death in immune suppressed or deficient patients. A vaccine against T. gondii is required to prevent consequences of the infection. The aim of this study is to generate a multivalent recombinant protein vaccine against T. gondii. METHODS: 49 previously discovered antigenic proteins of T gondii were evaluated by their expression level in E. coli and by comprehensive bioinformatics analyses to determine antigenic epitopes. Based on these analyses, six vaccine candidate proteins were selected to generate a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V. Humoral and cellular immune responses were determined by flow cytometry and ELISA. Vaccinated mice were challenged with T. gondii Ankara strain tachyzoites. RESULTS: In mice vaccinated with hexavalent vaccine, strong total IgG (P < 0.0001) and IgG2a (P < 0.001) responses were induced compared to controls, the ratio of CD4(+) and CD8(+) T lymphocytes secreting IFN-γ increased, and significantly higher extracellular IFN-γ secretion was achieved compared to the controls (P < 0.001). The survival time of the vaccinated mice increased to 8.38 ± 2.13 days which was significantly higher than controls (P < 0.01). CONCLUSIONS: Altogether, these results show that the hexavalent vaccine which is developed for the first time against T. gondii induced strong and balanced Th1 and Th2 immune responses as well as conferred significant protection against challenge with lethal toxoplasmosis in murine model.


id: cord-259669-fod4xkd7
title: The porcine dendritic cell family
author: Summerfield, Artur
date: 2008-06-06
txt: ./txt/cord-259669-fod4xkd7.txt
cache: ./cache/cord-259669-fod4xkd7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0145305X08001031
doi: 10.1016/j.dci.2008.05.005
summary:
  Being strategically located at sites of pathogen entry, such as mucosal surfaces and Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. Altogether, the co-expression of CD172a and CD1 along with relatively high levels of both CD80/86 and MHC class II represent phenotypic characteristics of porcine MoDC but no marker clearly differentiating them from monocyte-derived macrophages has been identified.

abstract:
  Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. As with the more extensively studied murine and human DCs, porcine DC can be generated from bone marrow haematopoietic cells or monocytes, and have been analysed in various immunological and non-immunological tissues. Both conventional DC (cDC) and plasmacytoid DC (pDC) have been characterized. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. These have been characterized in terms of the induction of DC maturation and pro-inflammatory, Th1-like or Th2-like cytokines secretion. Porcine pDC most effectively sense virus infections and are characterized by their capacity to produce large quantities of IFN-α and the pro-inflammatory cytokines TNF-α, IL-6 and IL-12. As such, the DC family as a whole is a powerful ally in the host battle against pathogen attack. Nevertheless, DC in particular tissue environments or under particular stimuli can down-regulate immune response development. This is not only important for preventing over-activation of the immune system and also for ensuring tolerance against self or “friendly” substances including food components, but may also be used as a mechanism of pathogens to evade immune responses.


id: cord-260485-o5wpcxdp
title: Conservation Genetics of the Cheetah: Genetic History and Implications for Conservation
author: Schmidt-Küntzel, Anne
date: 2018-01-12
url: https://api.elsevier.com/content/article/pii/B978012804088100006X
doi: 10.1016/b978-0-12-804088-1.00006-x
abstract:
  From allozymes in 1983 to whole genomes in 2015, genetic studies of the cheetah have been extensive. In this chapter we provide an overview of the available literature. Overall, patterns of genetic variation provided evidence of low variability and suggest this loss occurred thousands of years ago. Differences between published subspecies were supported genetically. At a local scale, populations were generally considered panmictic with minor genetic structure. Although cheetahs have persisted despite low genetic variability, important questions arise from these findings: Does the cheetah have the ability to adapt to and evolve with future changes in environmental and infectious pressure? How would cheetahs cope with further loss of genetic diversity? Connectivity in the wild should be maintained via prevention of habitat loss, while management of small isolated populations may require reestablishing gene flow. Genetics could assist captive-breeding decisions and provide forensic evidence as to the geographical origin of illegally traded animals.


id: cord-264401-9ogs55xr
title: Inferring the Urban Transmission Potential of Bat Influenza Viruses
author: Giotis, Efstathios S.
date: 2020-06-03
url: https://doi.org/10.3389/fcimb.2020.00264
doi: 10.3389/fcimb.2020.00264
abstract:
  Bats are considered natural reservoirs of various, potentially zoonotic viruses, exemplified by the influenza A-like viruses H17N10 and H18N11 in asymptomatic Neotropical bats. These influenza viruses are evolutionarily distinct, are poorly adapted to laboratory mice and ferrets and cannot reassort in vitro with conventional strains to form new influenza subtypes. However, they have attracted renewed attention following reports that their entry in host cells is mediated by the trans-species conserved MHC-II proteins, suggesting that they hold zoonotic potential. Despite the recent studies, the viruses' epidemiology and public health significance remain incompletely understood. Delineating the mechanistic basis of the interactions with their hosts and assessing their global distribution are essential in order to fully assess the zoonotic threat that these strains pose.


id: cord-267266-0lybzcz7
title: Dendritic cells: Immunological sentinels with a central role in health and disease
author: Stockwin, Luke H
date: 2000-04-01
txt: ./txt/cord-267266-0lybzcz7.txt
cache: ./cache/cord-267266-0lybzcz7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/10762408/
doi: 10.1046/j.1440-1711.2000.00888.x
summary:
  These ''danger'' or activation signals induce profound changes in dendritic cell physiology, facilitating the efficient stimulation of both adaptive and innate immunity. The DC are sensitive to a wide range of these stimuli that serve not only to activate innate immunity via the release of chemokines and proinflammatory mediators, but also trigger DC migration towards local lymphoid tissue in order to generate antigen-specific (adaptive) immunity. 37, 38 For the Langerhans cell, activation is also accompanied by the loss of specific markers, such as cutaneous lymphocyte antigen (CLA) and Birbeck granules, along with altered surface expression of cell adhesion molecules that facilitate movement into the afferent lymph. 138 Flt-3 is able to induce protective antitumour immunity in some animal models, 139, 140 which is thought to be a consequence of increased presentation of tumour antigens combined with increased NK cell activity. FcγR-mediated induction of dendritic cell maturation and MHC class I-restricted antigen presentation after immune complex internalisation

abstract:
  Immunological effector cells must be sensitive to the antigens or environmental signals that indicate that a pathogen is present. To this end, a group of cells known as the professional antigen‐presenting cells have the ability to educate T, B and NK cells as to the fingerprints of specific infections. The most adept of these cells are a closely related family termed dendritic cells (DC). A subset of these act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material combined with an ability to detect a wide variety of ‘danger’ signals. These ‘danger’ or activation signals induce profound changes in dendritic cell physiology, facilitating the efficient stimulation of both adaptive and innate immunity. In the present review, a number of recent advances in the understanding of DC biology are discussed. These advances offer insights into the pathogenesis of a wide variety of diseases and point towards future strategies for immunotherapy.


id: cord-269917-j0t8rjkc
title: Immunogenic properties of immunoglobulin superfamily members within complex biological networks
author: Odales, Josué
date: 2020-10-11
url: https://api.elsevier.com/content/article/pii/S0008874920303956
doi: 10.1016/j.cellimm.2020.104235
abstract:
  Antibodies, T cell receptors and major histocompatibility complex molecules are members of the immunoglobulin superfamily and have pivotal roles in the immune system. The fine interrelation between them regulates several immune functions. Here, we describe lesser-known functions ascribed to these molecules in generating and maintaining immune response. Particularly, we outline the contribution of antibody- and T cell receptor-derived complementarity-determining region neoantigens, antigenized antibodies, as well as major histocompatibility complex class I molecules-derived epitopes to the induction of protective/therapeutic immune responses against pathogens and cancer. We discuss findings of our own and other studies describing protective mechanisms, based on immunogenic properties of immunoglobulin superfamily members, and evaluate the perspectives of application of this class of immunogens in molecular vaccines design.


id: cord-273906-s7l0yxc0
author: Ranga, Vipin
date: 2020-07-23
url: https://doi.org/10.3390/vaccines8030408
doi: 10.3390/vaccines8030408
title:
  Immunogenic SARS-CoV-2 Epitopes: In Silico Study Towards Better Understanding of COVID-19 Disease—Paving the Way for Vaccine Development

abstract:
  The emergence of the COVID-19 outbreak at the end of 2019, caused by the novel coronavirus SARS-CoV-2, has, to date, led to over 13.6 million infections and nearly 600,000 deaths. Consequently, there is an urgent need to better understand the molecular factors triggering immune defense against the virus and to develop countermeasures to hinder its spread. Using in silico analyses, we showed that human major histocompatibility complex (MHC) class I cell-surface molecules vary in their capacity for binding different SARS-CoV-2-derived epitopes, i.e., short sequences of 8-11 amino acids, and pinpointed five specific SARS-CoV-2 epitopes that are likely to be presented to cytotoxic T-cells and hence activate immune responses. The identified epitopes, each one of nine amino acids, have high sequence similarity to the equivalent epitopes of SARS-CoV virus, which are known to elicit an effective T cell response in vitro. Moreover, we give a structural explanation for the binding of SARS-CoV-2-epitopes to MHC molecules. Our data can help us to better understand the differences in outcomes of COVID-19 patients and may aid the development of vaccines against SARS-CoV-2 and possible future outbreaks of novel coronaviruses.


id: cord-275433-58unu79x
title: Unveiling the roles of autophagy in innate and adaptive immunity
author: Levine, Beth
date: 2007
txt: ./txt/cord-275433-58unu79x.txt
cache: ./cache/cord-275433-58unu79x.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17767194/
doi: 10.1038/nri2161
summary:
  The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. The class III PI3K vPS34 (also known as PIK3C3) generates phosphatidylinositol-3-phosphate (PtdIns3P) by phosphorylating The cellular events during digestion of self constituents or intracellular pathogens follow three distinct stages: initiation (formation of the phagophore), elongation (growth and closure) and maturation of a double membrane autophagosome into an autolysosome. In principle, autophagy may function in the direct elimination of viruses (as shown in vitro), in the breakdown of host factors required for viral replication or the inhibition of innate immune signalling, and in the promotion of cell survival either by maintaining bioenergetics in virally infected cells or by removing toxic self or viral components. In addition, numerous viruses inhibit the PKR (IFN-inducible doublestranded-RNA-dependent protein kinase) antiviral signalling pathway that is required for the induction of autophagy in virally infected cells or activate the autophagy-inhibitory class I PI3K-AKT-mTOR signalling pathway 63 .

abstract:
  Cells digest portions of their interiors in a process known as autophagy to recycle nutrients, remodel and dispose of unwanted cytoplasmic constituents. This ancient pathway, conserved from yeast to humans, is now emerging as a central player in the immunological control of bacterial, parasitic and viral infections. The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. This Review describes the mechanisms of autophagy and highlights recent advances relevant to the role of autophagy in innate and adaptive immunity.


id: cord-275608-joyan7ij
title: Why must T cells be cross-reactive?
author: Sewell, Andrew K.
date: 2012-08-24
url: https://www.ncbi.nlm.nih.gov/pubmed/22918468/
doi: 10.1038/nri3279
abstract:
  Clonal selection theory proposed that individual T cells are specific for a single peptide–MHC antigen. However, the repertoire of αβ T cell receptors (TCRs) is dwarfed by the vast array of potential foreign peptide–MHC complexes, and a comprehensive system requires each T cell to recognize numerous peptides and thus be cross-reactive. This compromise on specificity has profound implications because the chance of any natural peptide–MHC ligand being an optimal fit for its cognate TCR is small, as there will almost always be more-potent agonists. Furthermore, any TCR raised against a specific peptide–MHC complex in vivo can only be the best available solution from the naive T cell pool and is unlikely to be the best possible solution from the substantially greater number of TCRs that could theoretically be produced. This 'systems view' of TCR recognition provides a plausible cause for autoimmune disease and substantial scope for multiple therapeutic interventions. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri3279) contains supplementary material, which is available to authorized users.


id: cord-277054-eq4obbte
author: Kaur, Manpreet
date: 2009-03-26
url: https://www.sciencedirect.com/science/article/pii/S0264410X0900200X
doi: 10.1016/j.vaccine.2009.01.128
title:
  Rabies DNA vaccine: No impact of MHC Class I and Class II targeting sequences on immune response and protection against lethal challenge

abstract:
  Rabies is progressive fatal encephalitis. WHO estimates 55,000 rabies deaths and more than 10 million PEP every year world-wide. A variety of cell-culture derived vaccines are available for prophylaxis against rabies. However, their high cost restricts their usage in developing countries, where such cases are most often encountered. This is driving the quest for newer vaccine formulations; DNA vaccines being most promising amongst them. Here, we explored strategies of antigen trafficking to various cellular compartments aiming at improving both humoral and cellular immunity. These strategies include use of signal sequences namely Tissue Plasminogen Activator (TPA), Ubiquitin (UQ) and Lysosomal-Associated Membrane Protein-1 (LAMP-1). TPA, LAMP-1 and their combination were aimed at enhancing the CD4(+) T cell and antibody response. In contrast, the UQ tag was utilized for enhancing CD8(+) response. The potency of modified DNA vaccines assessed by total antibody response, antibody isotypes, cytokine profile, neutralizing antibody titer and protection conferred against in vivo challenge; was enhanced in comparison to native unmodified vaccine, but the response elicited did not pertain to the type of target sequence and the directed arm of immunity. Interestingly, the DNA vaccines that had been designed to generate different type of immune responses yielded in effect similar response. In conclusion, our data indicate that the directing target sequence is not the exclusive deciding factor for type and extent of immune response elicited and emphasizes on the antigen dependence of immune enhancement strategies.


id: cord-279498-ez3yq7xi
title: Immune Response in the Brain: Glial Response and Cytokine Production
author: Suzumura, Akio
date: 2008-12-31
url: https://api.elsevier.com/content/article/pii/S1567744307100144
doi: 10.1016/s1567-7443(07)10014-4
abstract:
  Abstract Although the brain has been considered as an immunologically privileged site, the evidence to date suggests that this is no longer the case. Cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-3 induce class I major histocompatibility complex (MHC) antigen expression on neural cells. IFN-γ, the most potent inducer of MHC antigen, also induces class II MHC antigen expression on microglia and astrocytes, which enable them to function as antigen-presenting cells. Thus, in some pathological conditions, invading T cells can interact with neural cells to induce central nervous system (CNS) damage. Glial cells have also been shown to produce various cytokines and chemokines. Almost all cytokines and chemokines known to occur in the immune system are also produced in the CNS. In this chapter, the glial responses contributing to neuroimmune interactions are reviewed, with a focus on production and functions of cytokines in the CNS.


id: cord-279924-09uwhxs9
title: T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells
author: Plaisted, Warren C.
date: 2014-01-01
url: https://api.elsevier.com/content/article/pii/S0042682213006478
doi: 10.1016/j.virol.2013.11.025
abstract:
  Neural precursor cells (NPCs) are the subject of intense investigation for their potential to treat neurodegenerative disorders, yet the consequences of neuroinvasive virus infection of NPCs remain unclear. This study demonstrates that NPCs support replication following infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV). JHMV infection leads to increased cell death and dampens IFN-γ-induced MHC class II expression. Importantly, cytokines secreted by CD4+ T cells inhibit JHMV replication in NPCs, and CD8+ T cells specifically target viral peptide-pulsed NPCs for lysis. Furthermore, treatment with IFN-γ inhibits JHMV replication in a dose-dependent manner. Together, these findings suggest that T cells play a critical role in controlling replication of a neurotropic virus in NPCs, a finding which has important implications when considering immune modulation for NPC-based therapies for treatment of human neurologic diseases.


id: cord-281691-3tl7f6tt
title: Construction and functional test of a chicken MHC-I (BF2*15)/peptide tetramer
author: Liu, Guangliang
date: 2008-03-15
url: https://www.ncbi.nlm.nih.gov/pubmed/18077001/
doi: 10.1016/j.vetimm.2007.10.019
abstract:
  The major histocompatibility complex class I (MHC class I) peptide tetramer is a sensitive and valuable tool to evaluate antigen-specific cytotoxic T lymphocytes (CTLs) of many animal species. To date, no chicken MHC class I peptide tetramer has been reported. In this report, we describe construction and functional evaluation of a chicken MHC-I (BF2*15)/peptide tetramer. To construct the chicken MHC class I peptide tetramer, genes of the chicken MHC-I α chain (BF2*15) and β2 microglobulin (Chβ2m) were synthesized by RT-PCR from the total RNA of PBMCs and the signal sequences were deleted. The BF2*15 was then fused with the BirA substrate peptide (BSP) sequence at the C terminus. Next, the synthesized PCR products of BF2*15 and Chβ2m were cloned into the expression vector pET-28a (+) and expressed in Escherichia coli strain BL21 (DE3). Highly purified BF2*15-BSP heavy chain and Chβ2m were obtained by a Ni(2+) NTA column affinity purification, yielding approximately 1.6 mg of BF2*15-BSP and 2.4 mg of Chβ2m per 1 g of the pelleted bacteria. The purified BF2*15-BSP heavy chain and Chβ2m were refolded with synthetic peptide originated from infectious bronchitis virus nucleoprotein (IBV N(71–78)) in refolding buffer to generate the monomer of BF2*15/peptide complex. The monomer was then biotinylated and tetramerized using PE-labeled streptavidin. Upon functional evaluation of the construct by using flowcytometry, we observed that 3.65% of CTLs were specific to IBV nucleoprotein. This demonstrates that the CTL response of IBV-infected chicks could effectively be evaluated using the prepared MHC-I BF2*15/peptide tetramer.


id: cord-283035-tpqf458q
title: Analyses of the spleen proteome of chickens infected with Marek's disease virus
author: Thanthrige-Don, Niroshan
date: 2009-08-01
url: https://doi.org/10.1016/j.virol.2009.05.020
doi: 10.1016/j.virol.2009.05.020
abstract:
  Marek's disease virus (MDV), which causes a lymphoproliferative disease in chickens, is known to induce host responses leading to protection against disease in a manner dependent on genetic background of chickens and virulence of the virus. In the present study, changes in the spleen proteome at 7, 14 and 21 days post-infection in response to MDV infection were studied using two-dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified using one-dimensional liquid chromatography electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS). Comparative analysis of multiple gels revealed that the majority of changes had occurred at early stages of the disease. In total, 61 protein spots representing 48 host proteins were detected as either quantitatively (false discovery rate (FDR) ≤ 0.05 and fold change ≥ 2) or qualitatively differentially expressed at least once during different sampling points. Overall, the proteins identified in the present study are involved in a variety of cellular processes such as the antigen processing and presentation, ubiquitin–proteasome protein degradation (UPP), formation of the cytoskeleton, cellular metabolism, signal transduction and regulation of translation. Notably, early stages of the disease were characterized by changes in the UPP, and antigen presentation. Furthermore, changes indicative of active cell proliferation as well as apoptosis together with significant changes in cytoskeletal components that were observed throughout the experimental period suggested the complexity of the pathogenesis. The present findings provide a basis for further studies aimed at elucidation of the role of these proteins in MDV interactions with its host.


id: cord-285091-2i2v5ecg
title: The Role of Cysteine Proteinases and their Inhibitors in the Host-Pathogen Cross Talk
author: Kopitar-Jerala, Nataša
date: 2012-12-17
txt: ./txt/cord-285091-2i2v5ecg.txt
cache: ./cache/cord-285091-2i2v5ecg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23305363/
doi: 10.2174/138920312804871102
summary:
  showed that inhibitors of cysteine proteinases cystatin C and p41 form of major histocompatibility complex invariant chain did not inhibit cathepsin L and the authors suggested that cystatin F might be the inhibitor that selectively regulated cathepsin L activity in macrophages [69] . Gene targeting studies showed a critical role for the lysosomal cysteine protease cathepsin S in the late stages of Ii degradation in B cells, DCs and macrophages [89] [90] [91] and cathepsin L (V in humans) in thymic cortical epithelium [92] . An additional level of control is achieved by the proteolysis full length TLR7 and TLR9 by endosomal cysteine cathepsins and AEP.TLR9 can bind its ligand CpG DNA, but it cannot trigger activation signals without first being processed by endolysosomal proteases, which remove N-terminal region [98] [99] [100] [101] . The study shows that the functions of proteinases in the virus entry into the cell as well as in host immune response are relevant for the possible therapy with inhibitors.

abstract:
  Proteinases and their inhibitors play essential functional roles in basic biological processes in both hosts and pathogens. Endo/lysosomal cathepsins participate in immune response in pathogen recognition and elimination. They are essential for both antigen processing and presentation (host adaptive immune response) and activation of endosomal Toll like receptors (innate immune response). Pathogens can produce proteases and also natural inhibitors to subvert the host immune response. Several pathogens are sensed through the intracellular pathogen recognition receptors, but only some of them use the host proteolytic system to escape into the cytosol. In this review, I provide an update on the most recent developments regarding the role of proteinases and their inhibitors in the initiation and regulation of immune responses.


id: cord-289606-hypqpqs0
title: Activation of CD8 T Lymphocytes during Viral Infections
author: Sigal, Luis J.
date: 2016-05-09
url: https://www.sciencedirect.com/science/article/pii/B9780123742797140093
doi: 10.1016/b978-0-12-374279-7.14009-3
abstract:
  CD8 T lymphocytes are a major cell population of the adaptive immune system. A fundamental characteristic of the CD8 T lymphocyte pool is that it is composed of millions of clones; each with a unique T cell receptor capable of recognizing a limited number of peptides displayed at the cell surface bound to the grooves of major histocompatibility complex class I (MHC I) molecules. Naïve CD8 T lymphocytes are normally resting and circulate between the blood and secondary lymphoid organs in search of their cognate peptide–MHC complexes. During viral infections, bone marrow–derived professional antigen-presenting cells (pAPCs) in secondary lymphoid organs display viral peptides on their MHC I molecules. Specific CD8 T lymphocytes that recognize these peptide–MHC adducts become activated (primed), proliferate extensively, and develop into effectors capable of killing infected cells, identified by the presence at their surface of the pertinent viral peptide–MHC complexes. This article describes how the process of priming naïve CD8 T lymphocytes occurs.


id: cord-291070-y0wf456f
author: Zhang, Guang Lan
date: 2005-07-01
txt: ./txt/cord-291070-y0wf456f.txt
cache: ./cache/cord-291070-y0wf456f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15980450/
doi: 10.1093/nar/gki479
summary:
  PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED BALB/c is a computational system for the prediction of peptides binding to all five MHC molecules in BALB/c mice (H2 d ) class I (H2-K d , H2-L d and H2-D d ) and class II (I-A d and I-E d ) that allows analysis of proteins for the presence of binding motifs to all five H2 d molecules in parallel. We derived the initial quantitative matrices for PRED BALB/c using logarithmic equations based on the frequency of amino acids at specific positions within the training set of 9mer peptides as described previously (16) . To our knowledge, PRED BALB/c is the first online server for the prediction of peptides binding to a complete set of MHC molecules in a model organism (H2 d haplotype).

title:
  PRED(BALB/c): a system for the prediction of peptide binding to H2(d) molecules, a haplotype of the BALB/c mouse

abstract:
  PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED(BALB/c) is available at .


id: cord-292596-ulu5y140
author: Lee, Su Hae
date: 2020-07-29
url: https://doi.org/10.1186/s42826-020-00056-y
doi: 10.1186/s42826-020-00056-y
title:
  Characterization of changes in global gene expression in the hearts and kidneys of transgenic mice overexpressing human angiotensin-converting enzyme 2

abstract:
  Human angiotensin-converting enzyme 2 (hACE2) has recently received a great attention due to it play a critical role as SARS-CoV receptor in the infection of human body. However, no further analysis for gene regulation has been performed in target tissues of model mice during hACE2 overproduction. To characterize changes in global gene expression in the hearts and kidneys of rtTA/hACE2 double transgenic (dTg) mice in response to hACE2 overexpression, total RNA extracted from these tissues from dTg mice after doxycycline (Dox) treatment was hybridized to oligonucleotide microarrays. Briefly, dTg mice were generated by cross-mating pα-MHC/rtTA Tg mice with pTRE/hACE2 Tg mice. The expression level of hACE2 protein was determined to be high in hearts, kidneys, and brains of dTg mice, whereas lung, liver, and testis tissues expressed low levels. The level of hACE2 was significantly enhanced in hearts and kidneys of the Dox+dTg group compared to that in Vehicle+dTg mice although consistent levels of mouse ACE2 (mACE2) remained in the same tissues. Based on the microarray analysis of heart tissue, 385 genes were differentially expressed, including 168 upregulated and 217 downregulated, when comparing non-Tg and Vehicle+dTg mice, whereas 216 genes were differentially expressed, including 136 upregulated and 80 downregulated, between Vehicle+dTg and Dox+dTg mice. In the kidneys, 402 genes were differentially expressed, including 159 upregulated and 243 downregulated, between non-Tg and Vehicle+dTg mice. Dox-treated dTg mice exhibited the differential expression of 4735 genes including 1636 upregulated and 3109 downregulated. Taken together, these findings suggested that several functional groups and individual genes can be considered biomarkers that respond to hACE2 overexpression in dTg mice. Moreover, our results provided a lot of useful information to predict physiological responses when these dTg mice are applied as a susceptible model for novel coronavirus (SARS-CoV, COVID-19) in both vaccine and drug development.


id: cord-296347-fanlvxqs
title: Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions
author: Loureiro, Joana
date: 2006-12-02
url: https://api.elsevier.com/content/article/pii/S0065277606920069
doi: 10.1016/s0065-2776(06)92006-9
abstract:
  Relatively small genomes and high replication rates allow viruses and bacteria to accumulate mutations. This continuously presents the host immune system with new challenges. On the other side of the trenches, an increasingly well‐adjusted host immune response, shaped by coevolutionary history, makes a pathogen's life a rather complicated endeavor. It is, therefore, no surprise that pathogens either escape detection or modulate the host immune response, often by redirecting normal cellular pathways to their advantage. For the purpose of this chapter, we focus mainly on the manipulation of the class I and class II major histocompatibility complex (MHC) antigen presentation pathways and the ubiquitin (Ub)‐proteasome system by both viral and bacterial pathogens. First, we describe the general features of antigen presentation pathways and the Ub‐proteasome system and then address how they are manipulated by pathogens. We discuss the many human cytomegalovirus (HCMV)‐encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)‐membrane into the cytosol, a process termed ER dislocation. US2‐ and US11‐mediated subversion of ER dislocation ensures proteasomal degradation of class I MHC molecules and presumably allows HCMV to avoid recognition by cytotoxic T cells, whilst providing insight into general aspects of ER‐associated degradation (ERAD) which is used by eukaryotic cells to purge their ER of defective proteins. We discuss the similarities and differences between the distinct pathways co‐opted by US2 and US11 for dislocation and degradation of human class I MHC molecules and also a putatively distinct pathway utilized by the murine herpes virus (MHV)‐68 mK3 immunoevasin for ER dislocation of murine class I MHC. We speculate on the implications of the three pathogen‐exploited dislocation pathways to cellular ER quality control. Moreover, we discuss the ubiquitin (Ub)‐proteasome system and its position at the core of antigen presentation as proteolysis and intracellular trafficking rely heavily on Ub‐dependent processes. We add a few examples of manipulation of the Ub‐proteasome system by pathogens in the context of the immune system and such diverse aspects of the host–pathogen relationship as virus budding, bacterial chromosome integration, and programmed cell death, to name a few. Finally, we speculate on newly found pathogen‐encoded deubiquitinating enzymes (DUBs) and their putative roles in modulation of host–pathogen interactions.


id: cord-298169-2133gahl
author: Tamouza, Ryad
date: 2020-10-05
txt: ./txt/cord-298169-2133gahl.txt
cache: ./cache/cord-298169-2133gahl.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33031918/
doi: 10.1016/j.bbi.2020.09.033
summary:
  Despite evidence of prominent immune implication in a significant subset of major psychiatric disorder patients such as schizophrenia, bipolar disorder or depression (Khandaker, Dantzer, Jones, 2017) or autism spectrum disorder (Meltzer & Van de Water, 2017) , deciphering the mechanistic link between the HLA system and these disorders was difficult, primarily because of the complex genetic architecture of the HLA system. This section reviews investigations of HLA gene candidate association in schizophrenia, bipolar disorders and Autism Spectrum Disorders, focusing on the risk/protection that HLA alleles/haplotypes may confer on specific sub-groups. Influenza and other infections prenatally can also increase risk of schizophrenia and autism spectrum disorders in the offspring, suggesting that HLA/MHC genetic variations may interact with prenatal infection in the etiology of major psychiatric disorders, although complicated by the immune-suppression that occurs in pregnancy (Shah et al, 2010) .

title:
  Understanding the genetic contribution of the Human Leukocyte Antigen system to common major psychiatric disorders in a world pandemic context

abstract:
  The human leukocyte antigen (HLA) is a complex genetic system that encodes proteins which predominantly regulate immune/inflammatory processes. It can be involved in a variety of immuno-inflammatory disorders ranging from infections to autoimmunity and cancers. The HLA system is also suggested to be involved in neurodevelopment and neuroplasticity, especially through microglia regulation and synaptic pruning. Consequently, this highly polymorphic gene region has recently emerged as a major player in the etiology of several major psychiatric disorders, such as schizophrenia, autism spectrum disorder and bipolar disorder and with less evidence for major depressive disorders and attention deficit hyperactivity disorder. We thus review here the role of HLA genes in particular subgroups of psychiatric disorders and foresee their potential implication in future research. In particular, given the prominent role that the HLA system plays in the regulation of viral infection, this review is particularly timely in the context of the Covid-19 pandemic.


id: cord-299786-wuve0tjz
title: Manipulation of cell surface macromolecules by flaviviruses
author: Anderson, Robert
date: 2004-02-27
txt: ./txt/cord-299786-wuve0tjz.txt
cache: ./cache/cord-299786-wuve0tjz.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0065352703590078
doi: 10.1016/s0065-3527(03)59007-8
summary:
  Dengue virus infection of immature myeloid dendritic cells has been shown to induce their maturation accompanied by the expression of major histocompatibility complex (MHC) class I and II antigens; the costimulatory molecules CD40, CD80, and CD86; and the dendritic cell marker CD83 (Libraty et al., 2001) . Flaviviruses, including dengue and West Nile (Shen et al., 1997) viruses, activate endothelial cell adhesion molecule expression by either direct (virus-mediated) or indirect (cytokine-mediated) mechanisms (see Section V,C). A major candidate event in such a route is the activation of endothelial cell adhesion molecules by a factor(s) (particularly TNF-) produced by dengue virus-infected blood monocytes . Thus the roles of prior immunity, antibody-enhanced virus infection, and immune-mediated pathologic effects on the vascular system are key points in understanding the pathogenesis of dengue hemorrhagic disease. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes

abstract:
  Cell surface macromolecules play a crucial role in the biology and pathobiology of flaviviruses, both as receptors for virus entry and as signaling molecules for cell–cell interactions in the processes of vascular permeability and inflammation. This review examines the cell tropism and pathogenesis of flaviviruses from the standpoint of cell surface molecules, which have been implicated as receptors in both virus–cell as well as cell–cell interactions. The emerging picture is one that encompasses extensive regulation and interplay among the invading virus, viral immune complexes, Fc receptors, major histocompatibility complex antigens, and adhesion molecules.


id: cord-301293-jqy7lcbk
author: Gupta, Vandana
date: 2006-03-30
url: https://www.sciencedirect.com/science/article/pii/S004268220500783X
doi: 10.1016/j.virol.2005.11.042
title:
  SARS coronavirus nucleocapsid immunodominant T-cell epitope cluster is common to both exogenous recombinant and endogenous DNA-encoded immunogens

abstract:
  Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-γ and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-γ responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N(76–114), each of which contained nonameric H2(d) binding domains with high binding scores for both class I and, except for N(76–93), class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-γ and IL-4 responses and strong memory CTL responses to the LAMP-N chimera.


id: cord-303069-ss6g3jkg
title: An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2
author: Jakhar, Renu
date: 2020-05-26
txt: ./txt/cord-303069-ss6g3jkg.txt
cache: ./cache/cord-303069-ss6g3jkg.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.05.26.115790
doi: 10.1101/2020.05.26.115790
summary:
  A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. The aim of this study is to analyze envelope protein strains using in silico approaches looking for the conservancy, which is further studied to predict all potential epitopes that can be used after in vitro and in vivo confirmation as a therapeutic peptide vaccine [22, 23, 24] . Envelope protein from the SARS-CoV-2 was analyzed using the IEDB MHC-1 binding prediction tool to predict the T cell epitope suggested interacting with different types of MHC Class I alleles. Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus

abstract:
  COVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate.


id: cord-304635-z5vmhopa
author: Ji, Wei
date: 2019-06-18
txt: ./txt/cord-304635-z5vmhopa.txt
cache: ./cache/cord-304635-z5vmhopa.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.molimm.2019.06.005
doi: 10.1016/j.molimm.2019.06.005
summary:
  title: Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner However, based on the structures of a series of MHC I molecules, such as human HLA-B*2705 (Madden et al., 1991) , rhesus macaque Mamu-A*02 , and mouse H-2K d (Mitaksov and Fremont, 2006; Zhou et al., 2004) , there is a salt bridge positioned over the peptides formed by opposite charged residues from the α1 and α2 helices of MHC I, respectively. Herein, by determining the crystal structures of human MHC I HLA-B*4001 complexed with a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N)-derived T-cell epitope (Oh et al., 2011) and mouse MHC I H-2K d bound to an immunodominant T-cell epitope from human hepatitis B virus (HBV) core antigen (HBc) (Li et al., 2005) , we clearly demonstrated the molecular features of MHC I molecules with two different salt bridges formed by the residues pairs Arg62-Glu163 and Arg66-Glu163, respectively.

title:
  Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner

abstract:
  The viral peptides presentation by major histocompatibility complex class I (MHC I) molecules play a pivotal role in T-cell recognition and the subsequent virus clearance. This process is delicately adjusted by the variant residues of MHC I, especially the residues in the peptide binding groove (PBG). In a series of MHC I molecules, a salt bridge is formed above the N-terminus of the peptides. However, the potential impact of the salt bridge on peptide binding and T-cell receptor (TCR) recognition of MHC I, as well as the corresponding molecular basis, are still largely unknown. Herein, we determined the structures of HLA-B*4001 and H-2K(d) in which two different types of salt bridges (Arg62-Glu163 or Arg66-Glu163) across the PBG were observed. Although the two salt bridges led to different conformation shifts of both the MHC I α helix and the peptides, binding of the peptides with the salt bridge residues was relatively conserved. Furthermore, through a series of in vitro and in vivo investigations, we found that MHC I mutations that disrupt the salt bridge alleviate peptide binding and can weaken the TCR recognition of MHC I-peptide complexes. Our study may provide key references for understanding MHC I-restricted peptide recognition by T-cells.


id: cord-306096-2yl07bdq
title: Viruses and Autoimmune Diseases
author: OLDSTONE, M. B. A.
date: 2003-11-03
txt: ./txt/cord-306096-2yl07bdq.txt
cache: ./cache/cord-306096-2yl07bdq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/9350280/
doi: 10.1046/j.1365-3083.1997.d01-145.x
abstract: nan
summary:
  In the absence of viral infection, IDDM can be induced when such anergic CTL clones (of high or low affinity) in the periphery are activated as they pass into an islet environment where interferon-g or B7.1 are expressed [9, 10] . To examine whether molecular mimicry between a virus and a protein expressed in oligodendrocytes could lead to a central nervous system (CNS) autoimmune disease much like the demyelinating disease, multiple sclerosis, transgenic mice were generated whose oligodendrocytes expressed either the nucleoprotein or glycoprotein of a virus [41] . Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response Molecular mimicry in T-cell mediated autoimmunity: viral peptides activate human T-cell clones specific for myelin basic protein Oral insulin treatment suppresses virus-induced antigen-specific destruction of b cells and prevents autoimmune diabetes in transgenic mice


id: cord-306308-zjq6cscm
author: de Moura, Ronald Rodrigues
date: 2020-08-05
txt: ./txt/cord-306308-zjq6cscm.txt
cache: ./cache/cord-306308-zjq6cscm.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1136/jclinpath-2020-206946
doi: 10.1136/jclinpath-2020-206946
summary:
  Aiming at better understanding the biology of the infection and the immune response against the virus in the Brazilian population, we analysed SARS-CoV-2 protein S peptides in order to identify epitopes able to elicit an immune response mediated by the most frequent MHC-I alleles using in silico methods. METHODS: Our analyses consisted in searching for the most frequent Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-C alleles in the Brazilian population, excluding the genetic isolates; then, we performed: molecular modelling for unsolved structures, MHC-I binding affinity and antigenicity prediction, peptide docking and molecular dynamics of the best fitted MHC-I/protein S complexes. CONCLUSIONS: Being aware of the intrinsic limitations of in silico analysis (mainly the differences between the real and the Protein Data Bank (PDB) structure; and accuracy of the methods for simulate proteasome cleavage), we identified 24 epitopes able to interact with 17 MHC-I more frequent alleles in the Brazilian population that could be useful for the development of strategic methods for vaccines against SARS-CoV-2.

title:
  Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population

abstract:
  AIMS: Brazil is nowadays one of the epicentres of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and new therapies are needed to face it. In the context of specific immune response against the virus, a correlation between Major Histocompatibility Complex Class I (MHC-I) and the severity of the disease in patients with COVID-19 has been suggested. Aiming at better understanding the biology of the infection and the immune response against the virus in the Brazilian population, we analysed SARS-CoV-2 protein S peptides in order to identify epitopes able to elicit an immune response mediated by the most frequent MHC-I alleles using in silico methods. METHODS: Our analyses consisted in searching for the most frequent Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-C alleles in the Brazilian population, excluding the genetic isolates; then, we performed: molecular modelling for unsolved structures, MHC-I binding affinity and antigenicity prediction, peptide docking and molecular dynamics of the best fitted MHC-I/protein S complexes. RESULTS: We identified 24 immunogenic epitopes in the SARS-CoV-2 protein S that could interact with 17 different MHC-I alleles (namely, HLA-A*01:01; HLA-A*02:01; HLA-A*11:01; HLA-A*24:02; HLA-A*68:01; HLA-A*23:01; HLA-A*26:01; HLA-A*30:02; HLA-A*31:01; HLA-B*07:02; HLA-B*51:01; HLA-B*35:01; HLA-B*44:02; HLA-B*35:03; HLA-C*05:01; HLA-C*07:01 and HLA-C*15:02) in the Brazilian population. CONCLUSIONS: Being aware of the intrinsic limitations of in silico analysis (mainly the differences between the real and the Protein Data Bank (PDB) structure; and accuracy of the methods for simulate proteasome cleavage), we identified 24 epitopes able to interact with 17 MHC-I more frequent alleles in the Brazilian population that could be useful for the development of strategic methods for vaccines against SARS-CoV-2.


id: cord-307445-r2os3kn9
title: Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats
author: Lu, Dan
date: 2019-09-09
url: https://doi.org/10.1371/journal.pbio.3000436
doi: 10.1371/journal.pbio.3000436
abstract:
  Bats harbor many zoonotic viruses, including highly pathogenic viruses of humans and other mammals, but they are typically asymptomatic in bats. To further understand the antiviral immunity of bats, we screened and identified a series of bat major histocompatibility complex (MHC) I Ptal-N*01:01–binding peptides derived from four different bat-borne viruses, i.e., Hendra virus (HeV), Ebola virus (EBOV), Middle East respiratory syndrome coronavirus (MERS-CoV), and H17N10 influenza-like virus. The structures of Ptal-N*01:01 display unusual peptide presentation features in that the bat-specific 3–amino acid (aa) insertion enables the tight “surface anchoring” of the P1-Asp in pocket A of bat MHC I. As the classical primary anchoring positions, the B and F pockets of Ptal-N*01:01 also show unconventional conformations, which contribute to unusual peptide motifs and distinct peptide presentation. Notably, the features of bat MHC I may be shared by MHC I from various marsupials. Our study sheds light on bat adaptive immunity and may benefit future vaccine development against bat-borne viruses of high impact on humans.


id: cord-308043-h0knm8y4
title: Autophagy as an emerging dimension to adaptive and innate immunity
author: Hussey, Séamus
date: 2009-08-31
txt: ./txt/cord-308043-h0knm8y4.txt
cache: ./cache/cord-308043-h0knm8y4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.smim.2009.05.004
doi: 10.1016/j.smim.2009.05.004
summary:
  These lines of evidence suggest a more elaborate TLR control of autophagy whereby TLR-adapter molecules interact with proteins from the autophagic pathway rather than by simply activating the classic hierarchical signaling cascades described heretofore. The authors demonstrated that the Atg5-Atg12 conjugate negatively regulates the antiviral immune response by interacting with the RIG-I-like receptor (s protein retinoic acid-inducible gene I (RIG-I) and IFN-␤ promoter stimulator 1 (IPS-1) thus, implying autophagy contributes to viral replication. In another study, the same group demonstrated that the fusion of influenza matrix protein 1 (MP1) with Atg8/LC3 drives this molecule to autophagosomes in different cell types and enhances recognition by antigen specific CD4+ T cells [117] . Accordingly, Atg6 silencing dampened this process, while rapamycin treatment enhanced priming of 85B-specific CD4 + T cells, strongly suggesting a role for autophagy in MHC class II presentation of antigens of bacterial origin.

abstract:
  Abstract Autophagy is an evolutionary conserved cellular process during which cytoplasmic material is engulfed in double membrane vacuoles that then fuse with lysosomes, ultimately degrading their cargo. Emerging evidence, however, now suggests that autophagy can form part of our innate and adaptive immune defense programs. Recent studies have identified pattern recognition molecules as mediators of this process and shown that intracellular pathogens can interact with and even manipulate autophagy. Recent translational evidence has also implicated autophagy in the pathogenesis of several immune-mediated diseases, including Crohn disease. In this review, we present autophagy in the context of its role as an immune system component and effector and speculate on imminent and future research directions in this field.


id: cord-310194-f5jtufja
author: Benedictus, Lindert
date: 2014-12-17
url: https://doi.org/10.1186/s13567-014-0129-0
doi: 10.1186/s13567-014-0129-0
title:
  Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype

abstract:
  Bovine Neonatal Pancytopenia (BNP), a bleeding syndrome of neonatal calves, is caused by alloantibodies absorbed from the colostrum of particular cows. A commercial BVD vaccine is the likely source of alloantigens eliciting BNP associated alloantibodies. We hypothesized that the rare occurrence of BNP in calves born to vaccinated dams could be associated with genetic differences within dams and calves. We found that the development of BNP within calves was a heritable trait for dams, not for calves and had a high heritability of 19%. To elucidate which genes play a role in the development of BNP we sequenced candidate genes and characterized BNP alloantibodies. Alloantigens present in the vaccine have to be presented to the dam’s immune system via MHC class II, however sequencing of DRB3 showed no differences in MHC class II haplotype between BNP and non-BNP dams. MHC class I, a highly polymorphic alloantigen, is an important target of BNP alloantibodies. Using a novel sequence based MHC class I typing method, we found no association of BNP with MHC class I haplotype distribution in dams or calves. Alloantibodies were detected in both vaccinated BNP and non-BNP dams and we found no differences in alloantibody characteristics between these groups, but alloantibody levels were significantly higher in BNP dams. We concluded that the development of BNP in calves is a heritable trait of the dam rather than the calf and genetic differences between BNP and non-BNP dams are likely due to genes controlling the quantitative alloantibody response following vaccination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0129-0) contains supplementary material, which is available to authorized users.


id: cord-310252-0cdqhrcw
title: Chapter 7 IFN Inducibility of Major Histocompatibility Antigens in Tumors
author: Seliger, Barbara
date: 2008-12-03
url: https://www.ncbi.nlm.nih.gov/pubmed/19055946/
doi: 10.1016/s0065-230x(08)00407-7
abstract:
  Interferons represent a protein family with pleiotropic functions including immunomodulatory, cytostatic, and cytotoxic activities. Based on these effects, interferons are involved in innate as well as adaptive immunity, thereby shaping the tumor host immune responses. These cytokines, alone or in combination, have been successfully implemented for the treatment of some malignancies. However, it has been recently demonstrated that tumor cells could be resistant to interferon treatment, which may be associated with an escape of tumor cells from immune surveillance. Therefore, the aim of this chapter is to summarize the frequency of impaired interferon signal transduction, their underlying molecular mechanisms, and their clinical relevance.


id: cord-310395-ae2x2wpg
author: Vieira, G. F.
date: 2005-12-31
url: https://api.elsevier.com/content/article/pii/S0306987705002999
doi: 10.1016/j.mehy.2005.05.041
title:
  Immunodominant viral peptides as determinants of cross-reactivity in the immune system – Can we develop wide spectrum viral vaccines?

abstract:
  Summary When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular “viral patterns” seems to be important steps towards the development of wide spectrum viral vaccines.


id: cord-310563-71940dh7
author: Kumar, Ashutosh
date: 2019-02-12
url: https://www.sciencedirect.com/science/article/pii/S0198885918309868
doi: 10.1016/j.humimm.2019.02.008
title:
  A multiepitopic theoretical fusion construct based on in-silico epitope screening of known vaccine candidates for protection against wide range of enterobacterial pathogens

abstract:
  Enterobacterial pathogens that have acquired antibiotic resistance genes are a leading cause of community and hospital acquired infections. In such a situation vaccination is considered as a better option to prevent such infections. In the current study reverse vaccinology approach has been used to select peptides from already known immunogenic proteins to design a chimeric construct. We selected Yersiniabactin receptor of Escherichia coli UMN026 and Flagellin of Stenotrophomonas maltophila. B-cell linear epitopes were predicted using Bepipred prediction tool. Peptide binding with reference sets of 27 alleles of MHC class I and class II was also analyzed. The predicted peptides-MHC complexes were further validated using simulation dynamics. The in-silico construction of chimera was done by restriction mapping and codon optimization. Chimera was evaluated using the immunoinformatic approach as done for the selected proteins. From the 673 amino acids of FyuA protein, a region from 1 to 492 was selected for containing more linear epitopes and the processing scores obtained were significant for MHC class I and class II binding. Similarly, from Flagellin, a region between 60 and 328 amino acids was selected and the peptides present in the selected region showed lower percentile ranks for binding with MHC molecules. The simulation studies validated the predictions of peptide-MHC complexes. The selected gene fragments accommodating maximum part of these peptides were used to design a chimaeric construct of 2454 bp. From the immunoinformatic analysis, the chimera was found to be more immunogenic in terms of increased number of B-cell and T-cell epitopes along with increased coverage of global populations with allelic variability.


id: cord-313138-y485ev30
title: Defense genes missing from the flight division
author: Magor, Katharine E.
date: 2013-04-24
url: https://api.elsevier.com/content/article/pii/S0145305X13001146
doi: 10.1016/j.dci.2013.04.010
abstract:
  Birds have a smaller repertoire of immune genes than mammals. In our efforts to study antiviral responses to influenza in avian hosts, we have noted key genes that appear to be missing. As a result, we speculate that birds have impaired detection of viruses and intracellular pathogens. Birds are missing TLR8, a detector for single-stranded RNA. Chickens also lack RIG-I, the intracellular detector for single-stranded viral RNA. Riplet, an activator for RIG-I, is also missing in chickens. IRF3, the nuclear activator of interferon-beta in the RIG-I pathway is missing in birds. Downstream of interferon (IFN) signaling, some of the antiviral effectors are missing, including ISG15, and ISG54 and ISG56 (IFITs). Birds have only three antibody isotypes and IgD is missing. Ducks, but not chickens, make an unusual truncated IgY antibody that is missing the Fc fragment. Chickens have an expanded family of LILR leukocyte receptor genes, called CHIR genes, with hundreds of members, including several that encode IgY Fc receptors. Intriguingly, LILR homologues appear to be missing in ducks, including these IgY Fc receptors. The truncated IgY in ducks, and the duplicated IgY receptor genes in chickens may both have resulted from selective pressure by a pathogen on IgY FcR interactions. Birds have a minimal MHC, and the TAP transport and presentation of peptides on MHC class I is constrained, limiting function. Perhaps removing some constraint, ducks appear to lack tapasin, a chaperone involved in loading peptides on MHC class I. Finally, the absence of lymphotoxin-alpha and beta may account for the observed lack of lymph nodes in birds. As illustrated by these examples, the picture that emerges is some impairment of immune response to viruses in birds, either a cause or consequence of the host-pathogen arms race and long evolutionary relationship of birds and RNA viruses.


id: cord-319761-bu5pzbnv
title: Pleiotropic mechanisms of virus survival and persistence
author: Miller, Craig S.
date: 2005-07-16
txt: ./txt/cord-319761-bu5pzbnv.txt
cache: ./cache/cord-319761-bu5pzbnv.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1079210405002374
doi: 10.1016/j.tripleo.2005.03.017
summary:
  Accordingly, this review focuses on specific viral cell interactions that allow the virus to survive the cellular attack and evade the immune system, establish persistent infections, and cause chronic disease. 13, 14 Viruses regulate apoptosis by several mechanisms including the targeting of the tumor suppressor gene product p53, the Fas death receptor, and by producing caspase inhibitors and viral Bcl-2 homologs. 24, 25 The alpha herpesvirus HSV-1 encodes several antiapoptotic gene products (ie, ICP4, ICP27, c34.5, U s 3, gJ) [26] [27] [28] [29] [30] that modulate apoptosis at several levels, including antagonism of double-stranded RNA-activated protein kinase (PKR), a downstream induction molecule of the interferon signaling pathway 31, 32 Of note, all c-herpesviruses express viral homologues of cellular antiapoptotic genes, including 1 or 2 Bcl-2 homologues. In the majority of infections, viruses encode products that antagonize either the IFN signal transduction pathway or cellular proteins induced by IFN that are responsible for inhibiting virus replication (Fig 2) .

abstract:
  Viruses are enormously efficient infectious agents that have been implicated in causing human disease for centuries. Transmission of these pathogens continues to be from one life form to another in the form of isolated cases, epidemics, and pandemics. Each infection requires entry into a susceptible host, replication, and evasion of the immune system. Viruses are successful pathogens because they target specific cells for their attack, exploit the cellular machinery, and are efficient in circumventing and/or inhibiting key cellular events required of survival. This article reviews some of the advances that have taken place in human virology in the past 50 years, emphasizing mechanisms that contribute to, and are involved with, virus survival and persistence.


id: cord-319993-er3sm4u8
author: Terry, Frances E
date: 2015-01-02
url: https://doi.org/10.1586/14760584.2015.955478
doi: 10.1586/14760584.2015.955478
title:
  Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases

abstract:
  Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere.


id: cord-322575-3goj00ej
title: Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques
author: Karl, Julie A.
date: 2013-07-01
url: https://www.ncbi.nlm.nih.gov/pubmed/23696100/
doi: 10.1534/g3.113.006254
abstract:
  The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.


id: cord-329036-4bf8eiix
author: nan
date: 1994-09-01
url: https://www.ncbi.nlm.nih.gov/pubmed/8064222/
doi: nan
title:
  Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific

abstract:
  Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Changes in class I expression in infected cells may contribute to the immunopathogenesis of MHV infection in the CNS. In this communication, a large panel of MHV strains was tested for their ability to stimulate class I expression in primary astrocytes in vitro. The data show that the more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV-D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The Kb molecule was preferentially expressed over Db. By contrast, JHMV and several viral strains derived from it did not stimulate the expression of class I molecules. Assays of virus infectivity indicated that the class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultraviolet light abolished the class I-inducing activity, indicating that infectious virus is required for class I expression. These data also suggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by infected astrocytes. Finally, analyses of A59/JHMV recombinant viral strains suggest that class I-inducing activity resides in one of the A59 structural genes.


id: cord-331555-yqhzyqs3
author: Umemoto, Eric Y.
date: 2003-03-04
txt: ./txt/cord-331555-yqhzyqs3.txt
cache: ./cache/cord-331555-yqhzyqs3.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0008874903000261
doi: 10.1016/s0008-8749(03)00026-1
summary:
  title: Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection We sought to determine the effect of this infection on the shape and number of dendritic cells and other major histocompatibility complex (MHC) class II expressing cells in the airway mucosa of Wistar rats. pulmonis infection as a model of chronic inflammation to determine the time course of changes in shape, number, and distribution of MHC class II expressing cells in the airway mucosa, with a focus on the region beneath the airway epithelium where M. In pathogen-free rats, a network of MHC class II expressing cells, identified by their OX6 immunoreactivity, occupied a thin layer just beneath the epithelium of the tracheal mucosa (Fig. 1A) . pulmonis infection resulted in conspicuous changes in the shape, number, and distribution of MHC class II expressing cells in the tracheal mucosa.

title:
  Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection

abstract:
  Mycoplasma pulmonis infection in rodents causes a chronic inflammatory airway disease with a strong immunological component, leading to mucosal remodeling and angiogenesis. We sought to determine the effect of this infection on the shape and number of dendritic cells and other major histocompatibility complex (MHC) class II expressing cells in the airway mucosa of Wistar rats. Changes in the shape of subepithelial OX6 (anti-MHC class II)-immunoreactive cells were evident in the tracheal mucosa 2 days after intranasal inoculation with M. pulmonis. By 1 week, the shape of the cells had changed from stellate to rounded (mean shape index increased from 0.42 to 0.77). The number of OX6-positive cells was increased 6-fold at 1 week and 16-fold at 4 weeks. Coincident with these changes, many columnar epithelial cells developed OX6 immunoreactivity, which was still present at 4 weeks. We conclude that M. pulmonis infection creates a potent immunologic stimulus that augments and transforms the OX6-immunoreactive cell population in the airways by changing the functional state of airway dendritic cells, initiating an influx of MHC class II expressing cells, and activating expression of MHC class II molecules by airway epithelial cells.


id: cord-333309-21czobqy
title: ERAD and how viruses exploit it
author: Byun, Hyewon
date: 2014-07-03
txt: ./txt/cord-333309-21czobqy.txt
cache: ./cache/cord-333309-21czobqy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25071743/
doi: 10.3389/fmicb.2014.00330
summary:
  Interaction of lectin-type and other chaperones with ERAD substrates allows association with members of the protein disulfide isomerase (PDI) family, which generally are characterized by one or more thioredoxin-like motifs (CXXC; Brodsky and Skach, 2011) . In contrast to the rhomboid proteases, the Derlins lack proteolytic activity, suggesting that these proteins bind to ERAD substrates and target them to E3 ligases for ubiquitination and to p97 for membrane extraction (Brodsky, 2012) . These ubiquitin ligases are members of the cytosolic SCF (S-phase kinase-associated protein 1 (Skp1)-Cullin 1 (Cul1)-F-box) family, where the F-box components of the SCF complex recognize the N-glycans of the retrotranslocated substrate, e.g., Fbs1 and Fbs2 (Yoshida, 2007) . A proteasomal ATPase contributes to dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins

abstract:
  Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response.


id: cord-334592-54dofkxh
title: Autophagy in immunity and inflammation
author: Levine, Beth
date: 2011-01-20
txt: ./txt/cord-334592-54dofkxh.txt
cache: ./cache/cord-334592-54dofkxh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/nature09782
doi: 10.1038/nature09782
summary:
  Moreover, p62 is required for starvation and IFN-γ-induced targeting of Fau (and perhaps other ubiquitylated protein complexes) to mycobacteria-containing phagosomes, resulting in the generation of antimycobacterial Fau-derived peptides 42 .The role of p62 in innate immunity is probably evolutionarily ancient, as the Drosophila p62 orthologue REF(2)P was originally identified in a screen for modifiers of sigma virus replication 43 . The mechanisms by which autophagy genes mediate in vivo resistance to infection are not fully understood, but are likely to involve a combination of xenophagy, other autophagy-protein-dependent effects on microbial replication or survival, activation of innate and adaptive immune responses, and/or alterations in pathogen-induced cell death (Fig. 3 ).

abstract:
  Autophagy is an essential, homeostatic process by which cells break down their own components. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation. However, in complex multicellular organisms, the core molecular machinery of autophagy — the 'autophagy proteins' — orchestrates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Recent developments reveal a crucial role for the autophagy pathway and proteins in immunity and inflammation. They balance the beneficial and detrimental effects of immunity and inflammation, and thereby may protect against infectious, autoimmune and inflammatory diseases.


id: cord-334603-yt2pmxi3
author: de Sousa, Eric
date: 2020-07-18
txt: ./txt/cord-334603-yt2pmxi3.txt
cache: ./cache/cord-334603-yt2pmxi3.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.ijid.2020.07.016
doi: 10.1016/j.ijid.2020.07.016
summary:
  title: Mortality in COVID-19 disease patients: Correlating Association of Major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants Abstract As the 2019 (COVID-19) pandemic caused by the novel coronavirus, SARS-CoV-2 spreads globally, differences in adverse clinical management outcomes have been associated with associated with age >65years, male gender, and co-morbidities such as smoking, diabetes, hypertension, cardiovascular comorbidity and immunosuppression. HLA-DQB1*06:02 has been selected for increased resistance to Yersinia pestis in immigrants from Africa to Europe, engagement of CD4+ T-cells to HLA-DQB1*06:02 leads to increased, pro-inflammatory IL-17 production, independent of the MHC class II presented peptides (12) and confers increased risk to the development of anti-myelin directed autoimmune responses (13) . DRB3*02:02 is linked to Grave''s disease (44) , serum IgG antibodies to Chlamydia pneumoniae with essential hypertension (45) and acute necrotizing encephalopathy (46) In conclusion, there appears to be no selective pressure from MHC class I alleles for SARS-CoV-2 variants tested.

title:
  Mortality in COVID-19 disease patients: Correlating Association of Major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants

abstract:
  Abstract As the 2019 (COVID-19) pandemic caused by the novel coronavirus, SARS-CoV-2 spreads globally, differences in adverse clinical management outcomes have been associated with associated with age >65years, male gender, and co-morbidities such as smoking, diabetes, hypertension, cardiovascular comorbidity and immunosuppression. Ethnicity has been the focus of attention after data from the United Kingdom showed a disproportionate number of deaths among healthcare workers from black, Asian and other ethnic minority backgrounds (1). In addition to ethnicity, socio-economic factors, prior vaccinations and exposure to other coronaviruses, other factors need to be considered to explain geographical and regional variations in susceptibility, severity of clinical expression of COVID-19 disease and outcomes. In the United States there have been disproportionate COVID-19 death rates among African Americans at around 2.6 times higher than that of other groups. Although these data could be due to multiple cultural and socioeconomic factors an underlying genetic susceptibility to SARS-CoV-2 infection may be a factor.


id: cord-335342-u0ys2xcm
author: Zhang, Qian‐Jin
date: 2007-02-02
txt: ./txt/cord-335342-u0ys2xcm.txt
cache: ./cache/cord-335342-u0ys2xcm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17278102/
doi: 10.1002/ijc.22371
summary:
  11 The nature of the immune suppression may include secretion of immunosuppressive cytokines, 12 the expression of ligands (FAS-L) that initiate apoptosis in cytotoxic T-cells 13 and tumor variants that are deficient in antigen processing and presentation. As a consequence, specific cytotoxic T-cells generated by the vaccine protocol are unable to recognize and kill these tumor variants due to defective presentation of tumor associated antigen-derived peptides recognized by the CTLs. The MHC Class I restricted antigen presentation pathway consists of a number of genes encoded in the MHC Class I locus of human chromosome 6. [16] [17] [18] Conversely TAP1 expression has been associated with tumor infiltrating lymphocytes (TILs), a characteristic of good clinical outcome 8, 16, 19 and spontaneous regression of MAAs. 4 In our study, we examine the effect of the restoration of TAP1 expression on MHC Class I antigen surface expression in the murine MAA cell line, B16F10.

title:
  TAP expression reduces IL‐10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma

abstract:
  Many immune therapeutic strategies are under development for melanoma to treat metastatic disease and prevent disease reoccurrence. However, human melanoma cells are often deficient in antigen processing and this appears to play a role in their expansion and escape from immunosurveillance. For example, expression of the transporters associated with antigen processing (TAP1 and TAP2) is down‐regulated in the mouse melanoma cell line B16F10. This results in a lack of tumor‐associated antigen processing, low surface expression of MHC Class I molecules and low immunogenicity. We observe that restoration of TAP1 expression by transfection resurrects the processing and presentation of viral antigens, and the melanoma‐associated antigen, TRP‐2. Immunization with irradiated B16F10/rTAP1 transfected cells generates CTLs that are capable of killing B16F10/rTAP1 transfected targets and B16F10 targets deficient in TAP1. Furthermore, B16F10/rTAP1 transfectants grow at a significantly slower rate in mice than B16F10 cells. In an experimental model that closely recapitulates the clinical situation, treatment of B16F10 tumors in mice with a vaccinia virus vector expressing TAP1 also significantly decreases tumor growth in vivo. Furthermore, tumors treated with vaccinia TAP1 had significantly reduced numbers of immunosuppressive, CD3(+)/IL‐10 positive, tumor infiltrating lymphocytes. Therefore, TAP1 expression restores both antigen presentation and immunogenicity in B16F10 melanoma cells and concomitantly reduces immunosuppressive IL‐10 production at the local tumor site, thereby increasing immunosurveillance mechanisms against tumors. © 2007 Wiley‐Liss, Inc.


id: cord-336343-qbcb9qi3
author: Agarwal, Ajay
date: 2020-06-16
url: https://doi.org/10.1101/2020.06.16.154559
doi: 10.1101/2020.06.16.154559
title:
  in-silica Analysis of SARS-CoV-2 viral strain using Reverse Vaccinology Approach: A Case Study for USA

abstract:
  The recent pandemic of COVID19 that has struck the world is yet to be battled by a potential cure. Countless lives have been claimed due to the existing pandemic and the societal normalcy has been damaged permanently. As a result, it becomes crucial for academic researchers in the field of bioinformatics to combat the existing pandemic. The study involved collecting the virulent strain sequence of SARS-nCoV19 for the country USA against human host through publically available bioinformatics databases. Using in-silica analysis and reverse vaccinology, two leader proteins were identified to be potential vaccine candidates for development of a multi-epitope drug. The results of this study can provide further researchers better aspects and direction on developing vaccine and immune responses against COVID19. This work also aims at promoting the use of existing bioinformatics tools to faster streamline the pipeline of vaccine development. The Situation of COVID19 A new infection respiratory disease was first observed in the month of December 2019, in Wuhan, situated in the Hubei province, China. Studies have indicated that the reason of this disease was the emergence of a genetically-novel coronavirus closely related to SARS-CoV. This coronavirus, now named as nCoV-19, is the reason behind the spread of this fatal respiratory disease, now named as COVID-19. The initial group of infections is supposedly linked with the Huanan seafood market, most likely due to animal contact. Eventually, human-to-human interaction occurred and resulted in the transmission of the virus to humans. [13]. Since then, nCoV-19 has been rapidly spreading within China and other parts of World. At the time of writing this article (mid-March 2020), COVID-19 has spread across 146 countries. A count of 164,837 cases have been confirmed of being diagnosed with COVID-19, and a total of 6470 deaths have occurred. The cumulative cases have been depicting a rising trend and the numbers are just increasing. WHO has declared COVID-19 to be a “global health emergency”. [14]. Current Scenario and Objectives Currently, research is being conducted on a massive level to understand the immunology and genetic characteristics of the disease. However, no cure or vaccine of nCoV-19 has been developed at the time of writing this article. Though, nCoV-19 and SARS-CoV are almost genetically similar, the respiratory syndrome caused by both of them, COVID-19 and SARS respectively, are completely different. Studies have indicated that – “SARS was more deadly but much less infectious than COVID-19”. -World Health Organization


id: cord-339091-3xk2w0d2
title: Computer aided selection of candidate vaccine antigens
author: Flower, Darren R
date: 2010-11-03
txt: ./txt/cord-339091-3xk2w0d2.txt
cache: ./cache/cord-339091-3xk2w0d2.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1745-7580-6-s2-s1
doi: 10.1186/1745-7580-6-s2-s1
summary:
  The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. Initially, the pathogenic genome is scanned for "open reading frames" or ORFs. Once all ORFs have been identified, proteins are selected on the basis that they will be accessible to immune system surveillance, usually using some form of informatic-based prediction methodology or, more likely, set of methdologies. We shall below examine three key approaches: subcellular location prediction, sequence similarity, and empirical statistical approaches, typified by VaxiJen. For a protein to be accessible to surveillance by the immune system, it is often assumed to be physically external to the microbial organism or at least present on its surface rather than being sequestered away far from the roving eye of the immune system.

abstract:
  Immunoinformatics is an emergent branch of informatics science that long ago pullulated from the tree of knowledge that is bioinformatics. It is a discipline which applies informatic techniques to problems of the immune system. To a great extent, immunoinformatics is typified by epitope prediction methods. It has found disappointingly limited use in the design and discovery of new vaccines, which is an area where proper computational support is generally lacking. Most extant vaccines are not based around isolated epitopes but rather correspond to chemically-treated or attenuated whole pathogens or correspond to individual proteins extract from whole pathogens or correspond to complex carbohydrate. In this chapter we attempt to review what progress there has been in an as-yet-underexplored area of immunoinformatics: the computational discovery of whole protein antigens. The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. We begin our review by placing antigen prediction firmly into context, exploring the role of reverse vaccinology in the design and discovery of vaccines. We also highlight several competing yet ultimately complementary methodological approaches: sub-cellular location prediction, identifying antigens using sequence similarity, and the use of sophisticated statistical approaches for predicting the probability of antigen characteristics. We end by exploring how a systems immunomics approach to the prediction of immunogenicity would prove helpful in the prediction of antigens.


id: cord-340781-z348xbn0
author: Namvar, Ali
date: 2019-10-23
txt: ./txt/cord-340781-z348xbn0.txt
cache: ./cache/cord-340781-z348xbn0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31645650/
doi: 10.1038/s41598-019-51679-8
summary:
  Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 .

title:
  In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine

abstract:
  Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4(+) and CD8(+) T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development.


id: cord-344105-9bw9rm6e
title: Methods for sequence and structural analysis of B and T cell receptor repertoires
author: Teraguchi, Shunsuke
date: 2020-07-17
txt: ./txt/cord-344105-9bw9rm6e.txt
cache: ./cache/cord-344105-9bw9rm6e.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S2001037020303408
doi: 10.1016/j.csbj.2020.07.008
summary:
  After describing the recent sequencing technologies for immune receptor repertoires, we survey structural modeling methods for BCR and TCRs, along with methods for clustering such models. We review downstream analyses, including BCR and TCR epitope prediction, antibody-antigen docking and TCR-peptide-MHC Modeling. The Immcantation framework [18, 19] and TRUST (TCR repertoire utilities for solid tissue) [20] can be also used for the same purpose among many other available tools not covered here Though single chain information alone is usually not enough to explain the binding of the receptor to the target epitope, there are several methods applicable to bulk sequencing data. Based on the observation that there are specific positions in TCR CDR3 regions that contact antigen peptides and that the presence of particular sequence motifs can define TCR clusters, Glanville et al., developed the GLIPH (grouping of lymphocyte interactions by paratope hotspots) algorithm [63, 64] .

abstract:
  B cell receptors (BCRs) and T cell receptors (TCRs) make up an essential network of defense molecules that, collectively, can distinguish self from non-self and facilitate destruction of antigen-bearing cells such as pathogens or tumors. The analysis of BCR and TCR repertoires plays an important role in both basic immunology as well as in biotechnology. Because the repertoires are highly diverse, specialized software methods are needed to extract meaningful information from BCR and TCR sequence data. Here, we review recent developments in bioinformatics tools for analysis of BCR and TCR repertoires, with an emphasis on those that incorporate structural features. After describing the recent sequencing technologies for immune receptor repertoires, we survey structural modeling methods for BCR and TCRs, along with methods for clustering such models. We review downstream analyses, including BCR and TCR epitope prediction, antibody-antigen docking and TCR-peptide-MHC Modeling. We also briefly discuss molecular dynamics in this context.


id: cord-346032-188gnf8j
author: Cheung, Ying-Kit
date: 2007-08-10
url: https://api.elsevier.com/content/article/pii/S0264410X07005932
doi: 10.1016/j.vaccine.2007.05.025
title:
  Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope

abstract:
  The severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV N) is one of the major targets for SARS vaccine due to its high potency in triggering immune responses. In this study, we have identified a novel HLA-A*0201 restricted epitope, N220 (LALLLLDRL), of the SARS-CoV N-protein through bioinformatics analysis. The N-protein peptide N220 shows a high binding affinity towards human MHC class I in T2-cells, and is capable of activating cytotoxic T-cells in human peripheral blood mononuclear cells (PBMCs). The application of using the N220 peptide sequence with a single-chain-trimer (SCT) approach to produce a potential DNA vaccine candidate was investigated in HLA-A2.1K(b) transgenic mice. Cytotoxicity assay clearly showed that the T-cells obtained from the vaccinated animals were able to kill the N-protein expressing cells with a cytotoxicity level of 86% in an effector cells/target cells ratio of 81:1 one week after the last vaccination, which is significantly higher than other N-protein peptides previously described. The novel immunogenic N-protein peptide revealed in the present study provides valuable information for therapeutic SARS vaccine design.


id: cord-347039-eap592i7
title: Maneuvering for advantage: the genetics of mouse susceptibility to virus infection
author: Lee, Seung-Hwan
date: 2003-08-31
txt: ./txt/cord-347039-eap592i7.txt
cache: ./cache/cord-347039-eap592i7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168952503001720
doi: 10.1016/s0168-9525(03)00172-0
summary:
  Receptors are recognized as important determinants of virus host range and tissue tropism; and some host resistance/susceptibility loci encode molecules that are expressed on the cell surface. Another example of natural host resistance is the restriction of ecotropic Murine LEUKEMIA VIRUS (MuLV) infection by the mouse Fv4 gene. The effort to understand the genetic basis of susceptibility to viral disease is driven by three considerations: (1) the increased public awareness of the toll imposed by viruses on the host; (2) the increase in susceptible human populations because of longer life expectancy, frequently accompanied by chronic illness, and the consequences of advances in medical technology, including immunosuppressive therapies for organ transplantation or treatment of malignancy; and (3) the need to develop new therapies for infections caused by multidrug-resistant Human killer-cell immunoglobulin-type receptor (KIR) is considered to be a functional homolog of mouse Ly49. Mouse genetics has also demonstrated that recognition and destruction of virus-infected cells by NK cells is mediated by specific interactions between activating NKcell receptors and viral target molecules.

abstract:
  Abstract Genetic studies of host susceptibility to infection contribute to our understanding of an organism's response to pathogens at the immunological, cellular, and molecular levels. In this review we describe how the study of host genetics in mouse models has helped our understanding of host defense mechanisms against viral infection, and how this knowledge can be extended to human infections. We focus especially on the innate mechanisms that function as the host's first line of defense against infection. We also discuss the main issues that confront this field, as well as its future.


id: cord-347298-7kqrl3rv
title: Immunology of the Testis and Male Reproductive Tract
author: Hedger, M.P.
date: 2010-07-12
url: https://api.elsevier.com/content/article/pii/B978008046884601112X
doi: 10.1016/b978-0-08-046884-6.01112-x
abstract:
  A large body of evidence points to the existence of a close, dynamic relationship between the immune system and the male reproductive tract, which has important implications for our understanding of both systems. The testis and the male reproductive tract provide an environment that protects the otherwise highly immunogenic spermatogenic cells and sperm from immunological attack. At the same time, secretions of the testis, including androgens, influence the development and mature functions of the immune system. Activation of the immune system has negative effects on both androgen and sperm production, so that systemic or local infection and inflammation compromise male fertility. The mechanisms underlying these interactions have begun to receive the attention from reproductive biologists and immunologists that they deserve, but many crucial details remain to be uncovered. A complete picture of male reproductive tract function and its response to toxic agents is contingent upon continued exploration of these interactions and the mechanisms involved.


id: cord-349225-504kr50e
title: Viral mechanisms of immune evasion
author: Alcami, Antonio
date: 2000-09-01
url: https://api.elsevier.com/content/article/pii/S1357431000017755
doi: 10.1016/s1357-4310(00)01775-5
abstract:
  During the millions of years they have coexisted with their hosts, viruses have learned how to manipulate host immune control mechanisms. Viral gene functions provide an overview of many relevant principles in cell biology and immunology. Our knowledge of viral gene functions must be integrated into virus–host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.


id: cord-350083-kldu8q8x
author: Oany, Arafat Rahman
date: 2015-08-08
txt: ./txt/cord-350083-kldu8q8x.txt
cache: ./cache/cord-350083-kldu8q8x.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s40203-015-0011-4
doi: 10.1186/s40203-015-0011-4
summary:
  title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. To date, information regarding the processing, structure and functions of Ebola virus (EBOV) protein L (EBOL) demonstrates that it is an RNA-dependent RNA polymerase, with the assistance of VP35. In the present study, we have followed immunoinformatics approaches for designing potential conserved epitope candidate for the utility of vaccine development against the deadly Ebola virus, with an expectation of further wet lab validation. Protein variability server predicted the variability of the conserved region of the RNA-dependent RNA polymerase-L ( Fig. 10) to ensure that the proposed epitope is within the invariable region. Design of an epitope-based peptide vaccine against spike protein of human corona virus: an in silico approach

title:
  Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach

abstract:
  PURPOSE: Ebola virus (EBOV) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. Although, medical technology has tried to handle the problems, there is no Food and Drug Administration (FDA)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of Ebola virus disease (EVD). METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. BioEdit v7.2.3 sequence alignment editor, Jalview v2 and CLC Sequence Viewer v7.0.2 were used for the initial sequence analysis for securing the conservancy from the sequences. Later the Immune Epitope Database and Analysis Resource (IEDB-AR) was used for the identification of T-cell and B-cellepitopes associated with type I and II major histocompatibility complex molecules analysis. Finally, the population coverage analysis was employed. RESULTS: The core epitope “FRYEFTAPF” was found to be the most potential one, with 100 % conservancy among all the strains of EBOV. It also interacted with both type I and II major histocompatibility complex molecules and is considered as nonallergenic in nature. Finally, with impressive cumulative population coverage of 99.87 % for the both MHC-I and MHC-II class throughout the world population was found for the proposed epitope. CONCLUSION: To end, the projected peptide gave us a solid stand to propose for vaccine consideration and that might be experimented for its potency in eliciting immunity through humoral and cell mediated immune responses in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40203-015-0011-4) contains supplementary material, which is available to authorized users.


id: cord-350583-0t1kly3i
author: Salmier, Arielle
date: 2016-10-26
url: https://www.ncbi.nlm.nih.gov/pubmed/27782798/
doi: 10.1186/s12862-016-0802-1
title:
  Spatial pattern of genetic diversity and selection in the MHC class II DRB of three Neotropical bat species

abstract:
  BACKGROUND: Although bats are natural reservoirs of many pathogens, few studies have been conducted on the genetic variation and detection of selection in major histocompatibility complex (MHC) genes. These genes are critical for resistance and susceptibility to diseases, and host–pathogen interactions are major determinants of their extensive polymorphism. Here we examined spatial patterns of diversity of the expressed MHC class II DRB gene of three sympatric Neotropical bats, Carollia perspicillata and Desmodus rotundus (Phyllostomidae), and Molossus molossus (Molossidae), all of which use the same environments (e.g., forests, edge habitats, urban areas). Comparison with neutral marker (mtDNA D-loop) diversity was performed at the same time. RESULTS: Twenty-three DRB alleles were identified in 19 C. perspicillata, 30 alleles in 35 D. rotundus and 20 alleles in 28 M. molossus. The occurrence of multiple DRB loci was found for the two Phyllostomidae species. The DRB polymorphism was high in all sampling sites and different signatures of positive selection were detected depending on the environment. The patterns of DRB diversity were similar to those of neutral markers for C. perspicillata and M. molossus. In contrast, these patterns were different for D. rotundus for which a geographical structure was highlighted. A heterozygote advantage was also identified for this species. No recombination or gene conversion event was found and phylogenetic relationships showed a trans-species mode of evolution in the Phyllostomids. CONCLUSIONS: This study of MHC diversity demonstrated the strength of the environment and contrasting pathogen pressures in shaping DRB diversity. Differences between positively selected sites identified in bat species highlighted the potential role of gut microbiota in shaping immune responses. Furthermore, multiple geographic origins and/or population admixtures observed in C. perspicillata and M. molossus populations acted as an additional force in shaping DRB diversity. In contrast, DRB diversity of D. rotundus was shaped by environment rather than demographic history. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-016-0802-1) contains supplementary material, which is available to authorized users.


id: cord-350772-fp5d9if0
author: Malone, Karen E.
date: 2008-01-18
url: https://doi.org/10.1002/glia.20625
doi: 10.1002/glia.20625
title:
  Induction of class I antigen processing components in oligodendroglia and microglia during viral encephalomyelitis

abstract:
  Glia exhibit differential susceptibility to CD8 T cell mediated effector mechanisms during neurotropic coronavirus infection. In contrast to microglia, oligodendroglia are resistant to CD8 T cell perforin‐mediated viral control in the absence of IFNγ. Kinetic induction of MHC Class I expression by microglia and oligodendroglia in vivo was thus analyzed to assess responses to distinct inflammatory signals. Flow cytometry demonstrated delayed Class I surface expression by oligodendroglia compared with microglia. Distinct kinetics of Class I protein upregulation correlated with cell type specific transcription patterns of genes encoding Class I heavy chains and antigen processing components. Microglia isolated from naïve mice expressed high levels of these mRNAs, whereas they were near detection limits in oligodendroglia; nevertheless, Class I protein was undetectable on both cell types. Infection induced modest mRNA increases in microglia, but dramatic transcriptional upregulation in oligodendroglia coincident with IFNα or IFNγ mRNA increases in infected tissue. Ultimately mRNAs reached similar levels in both cell types at their respective time points of maximal Class I expression. Expression of Class I on microglia, but not oligodendroglia, in infected IFNγ deficient mice supported distinct IFN requirements for Class I presentation. These data suggest an innate immune preparedness of microglia to present antigen and engage CD8 T cells early following infection. The delayed, yet robust, IFNγ dependent capacity of oligodendroglia to express Class I suggests strict control of immune interactions to avoid CD8 T cell recognition and potential presentation of autoantigen to preserve myelin maintenance. © 2008 Wiley‐Liss, Inc.


id: cord-352150-ey9kc7zj
author: Degauque, Nicolas
date: 2016-03-24
url: https://doi.org/10.3389/fimmu.2016.00089
doi: 10.3389/fimmu.2016.00089
title:
  Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation

abstract:
  Being able to track donor reactive T cells during the course of organ transplantation is a key to improve the graft survival, to prevent graft dysfunction, and to adapt the immunosuppressive regimen. The attempts of transplant immunologists have been for long hampered by the large size of the alloreactive T cell repertoire. Understanding how self-TCR can interact with allogeneic MHC is a key to critically appraise the different assays available to analyze the TCR Vβ repertoire usage. In this report, we will review conceptually and experimentally the process of cross-reactivity. We will then highlight what can be learned from allotransplantation, a situation of artificial cross-reactivity. Finally, the low- and high-resolution techniques to characterize the TCR Vβ repertoire usage in transplantation will be critically discussed.


id: cord-353877-wzndpcq3
author: Albagi, Sahar Obi Abd
date: 2020-05-20
url: https://doi.org/10.1101/2020.05.20.106351
doi: 10.1101/2020.05.20.106351
title:
  A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach

abstract:
  Due to the current COVID-19 pandemic, the rapid discovery of a safe and effective vaccine is an essential issue, consequently, this study aims to predict potential COVID-19 peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. To achieve this goal, several Immune Epitope Database (IEDB) tools, molecular docking, and safety prediction servers were used. According to the results, The Spike peptide peptides SQCVNLTTRTQLPPAYTNSFTRGVY is predicted to have the highest binding affinity to the B-Cells. The Spike peptide FTISVTTEI has the highest binding affinity to the MHC I HLA-B1503 allele. The Nucleocapsid peptides KTFPPTEPK and RWYFYYLGTGPEAGL have the highest binding affinity to the MHC I HLA-A0202 allele and the three MHC II alleles HLA-DPA1*01:03/DPB1*02:01, HLA-DQA1*01:02/DQB1- *06:02, HLA-DRB1, respectively. Furthermore, those peptides were predicted as non-toxic and non-allergen. Therefore, the combination of those peptides is predicted to stimulate better immunological responses with respectable safety.


id: cord-354030-8tfg881h
title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches
author: Dong, Rong
date: 2020-07-28
url: https://doi.org/10.3389/fimmu.2020.01784
doi: 10.3389/fimmu.2020.01784
abstract:
  COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1–14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.


id: cord-355075-ieb35upi
title: The immune gene repertoire of an important viral reservoir, the Australian black flying fox
author: Papenfuss, Anthony T
date: 2012-06-20
txt: ./txt/cord-355075-ieb35upi.txt
cache: ./cache/cord-355075-ieb35upi.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1471-2164-13-261
doi: 10.1186/1471-2164-13-261
summary:
  alecto transcriptome provides information on a variety of immune genes not previously identified in any bat species and represents an important starting point for examining the antiviral activity of these molecules. To enrich for sequences corresponding to cytokines and innate immune genes, the second dataset was derived from pooled total RNA obtained from mitogen-stimulated spleen, white blood cells and lymph node and unstimulated thymus and bone marrow obtained from one pregnant female and one adult male flying fox. A full length transcript, encoding a 667 amino acid protein was identified in our bat transcriptome datasets and found to be orthologous to Mx1 based on comparison with known mammalian Mx1 and Mx2 family members (Figure 4a and data not shown). Genes involved in the adaptive immune system, including MHC class I and II genes and T and B cell receptors and co-receptors were highly represented in both the thymus and pooled datasets providing evidence that bats have all of the components necessary to mount an adaptive immune response.

abstract:
  BACKGROUND: Bats are the natural reservoir host for a range of emerging and re-emerging viruses, including SARS-like coronaviruses, Ebola viruses, henipaviruses and Rabies viruses. However, the mechanisms responsible for the control of viral replication in bats are not understood and there is little information available on any aspect of antiviral immunity in bats. Massively parallel sequencing of the bat transcriptome provides the opportunity for rapid gene discovery. Although the genomes of one megabat and one microbat have now been sequenced to low coverage, no transcriptomic datasets have been reported from any bat species. In this study, we describe the immune transcriptome of the Australian flying fox, Pteropus alecto, providing an important resource for identification of genes involved in a range of activities including antiviral immunity. RESULTS: Towards understanding the adaptations that have allowed bats to coexist with viruses, we have de novo assembled transcriptome sequence from immune tissues and stimulated cells from P. alecto. We identified about 18,600 genes involved in a broad range of activities with the most highly expressed genes involved in cell growth and maintenance, enzyme activity, cellular components and metabolism and energy pathways. 3.5% of the bat transcribed genes corresponded to immune genes and a total of about 500 immune genes were identified, providing an overview of both innate and adaptive immunity. A small proportion of transcripts found no match with annotated sequences in any of the public databases and may represent bat-specific transcripts. CONCLUSIONS: This study represents the first reported bat transcriptome dataset and provides a survey of expressed bat genes that complement existing bat genomic data. In addition, these data provide insight into genes relevant to the antiviral responses of bats, and form a basis for examining the roles of these molecules in immune response to viral infection.


