cord-000224-2lz03oqb	2010	
cord-000488-x5ardo5j	2011	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. Recombinant constructs encoding chimeric and SLA-1*0401 molecules A synthetic gene encoding a transmembrane-truncated fragment encompassing residues 1 to 275 of human HLA-A*11:01 alpha chain followed by a FXa-BSP-HAT tag (FXa = factor Xa cleavage site comprised of the amino acid sequence IEGR, BSP = biotinylation signal peptide, HAT = histidine affinity tag for purification purposes; see Online Resource 1) had previously been generated and inserted into the pET28 expression plasmid (Novagen) (Ferre et al.
cord-001247-pxzbirqd	2014	Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients. To identify immune-dominant HBV-specific CTL epitopes, especially epitopes from HBc protein, is therefore necessary for monitoring T cell responses during disease progression, as well as for developing epitope-based therapeutic vaccines against CHB (Inchauspe and Michel, 2007; Gordon et al., 2013; Liu et al., 2013a, b) . To further determine the epitope-specific CTLs, fresh PBMCs from HLA-A2 + AHB patients were stimulated with HBc141-149 peptide and detected by ex vivo IFN-γ ELISPOT assays. In this study, we identified a new HLA-A2-restricted CD8 + T cell epitope HBc141-149 by screening an overlapping 9-mer peptide pool covering HBV core protein.
cord-002463-qhtj1pef	2017	Top scored eiptope subjected to 100 ns MD simulation **RMSF **RMSD **Hydrogen bond occupency analysis Secquence, having highest vaxijen score Prediction of B cell epitope, using-**T cell epitope prediction by proteasomal C terminal cleavage, TAP transport efficiency and MHC class 1 binding **Epitopes with IC50 value less than 50 for their binding to MHC class 1 molecule from IEDB analysis along with binding to highest number of alleles in both analyses were chosen **Epitope conservancy analysis **Population coverage analysis **Kolaskar and Tongaonkar antigenicity scale 48 **Emini surface accessibility prediction 47 **Karplus and Schulz flexibility prediction 49 **Bepipred linear epitope prediction 50 **Chou and Fasman beta turn prediction 52 Vaxijen analysis with a threshold score of >0. We also validated each epitope by molecular docking simulation and MM-GBSA/MM-PBSA studies with HLA-A*32:15 protein, as it was found common in the results from MHC-I binding interaction analysis.
cord-002686-zzongyfa	2017	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. 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. The generalized modules of membrane antigen-(GMMA-) based outer membrane proteins including SigA were also shown to be highly immunogenic [12] , which prompted us to target SigA as one of the best vaccine candidates and to design potential peptide vaccine covering all the Shigella spp. The SigA protein sequences of different strains of Shigella species were retrieved from the NCBI GenBank [22] database and analysed in the VaxiJen v2.0 [23] server for the determination of the most potent antigenic protein. IEDB analysis resource predicted both MHC class I-and MHC class II-based coverage of the selected epitopes for the world population to assess the feasibility of being a potential vaccine candidate.
cord-002704-cpa2sl50	2017	
cord-002724-gtv9syzi	2017	
cord-003143-n6b0r92e	2018	
cord-003270-vu9b5a14	2018	
cord-003472-ml4pbewf	2019	
cord-004395-erqmbi2b	2020	
cord-004435-l66ost6q	2020	Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/re-emerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines'' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. 13 An approach that must accommodate many factors affecting vaccine development like pathogen antigenic variability, the emergence of infectious disease, human genetic variation is the goal of immunoinformatics [ Figure 1 ]. 110 The surface glycoprotein can be regarded as antigen and hence can serve as a target for the immune system which if sequenced, using the new immunoinformatics approach and a common site for the varying proteins identified, a potent vaccine can be developed which can accommodate the antigenic drift/shifts of the virus.
cord-005453-4057qib7	2019	To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective, observational cohort study enrolled in 21 HID-SCT and 13 MSD-SCT recipients. The aim of this study is to identify the prognostic impact of pre-transplant TIM3 levels on early and late transplant related complications as well as post-transplant relapse and survival Methods: A total of 177 hematopoietic stem cell transplantation (HSCT) recipients with an initial diagnosis of acute leukemia [median age: 36(16-66) years; male/ female: 111/66] were included in the study.
cord-005460-ezrn8cva	2017	Still the optimal combination of immunosuppressive agents with PTCy should be elucidated for different types of SCTs. We report the 2-year update of the prospective NCT02294552 single-center trial that evaluated risk-adapted graft-versushost disease (GVHD) prophylaxis with PTCy in related, unrelated and haploidentical SCTs. 200 adult patients (median age 32 y.o., range: 18-62) with hematologic malignancies, including AML (47.5%), ALL (26.5%), CML (10.5%), MDS (4%), and lymphomas (11.5%), were enrolled in the study. Long-term follow-up from the prospective randomized phase III multicenter trial comparing a standard GvHD prophylaxis with cyclosporine A and methotrexate with or without additional pretransplant ATLG (Grafalon, previously ATG-FRESENIUS S) (given 20 mg/kg/day, days − 3 to − 1) in unrelated donor hematopoietic cell transplantation after myeloablative conditioning resulted in a significant reduction of acute and chronic GvHD without compromising relapse rate and survival [1, 2, 3] .
cord-005478-5iu38pr6	2019	There were some differences among groups: patients in group-1 were younger (median age 46 years, p< 0.02) were transplanted in more recent year (2015, p< 0.001), received more frequently a regimen based on TBF (thiotepa, fludarabine and busulfan) (83%, p< 0.001) and bone marrow (BM) as source of stem cells (77%, p< 0.001), with no ATG (100%, p< 0.001). Clinical Trial Registry: NCT01217723 Disclosure: None of the Authors have any conflicts of interest to declare O105 Immune reconstitution -based score at diagnosis of CGVHD predicts GVHD severity and overall-survival: A novel prognostication tool for GVHD treatment tailoring Background: Allogeneic stem cell transplantation (HSCT) survivors are at a relevant risk of developing chronic GvHD (cGvHD), which importantly affects quality of life and increases morbidity and mortality.
cord-005480-yg7salqt	2008	Standard NIH or Eurolupus cyclophosphamide (CY) protocols and mycophenolate Mofetil (MMF) as induction therapy in severe BILAG A SLE is still associated with 20 % failure, 50% relapse and 10% to 15 % death at 10 years In the absence of a single standard treatment worldwide for refractory SLE, phase I-II studies analysed the use of: a) rituximab (anti CD20 mAb) in more than 1 000 patients showing complete to partial early response around 100% with relapse in 50 to 60% of the cases; b) autologous Hematopoietic Stem Cell Transplantation (HSCT) since 1997 under the auspices of the joined EBMT-EULAR working party, reporting durable remission with reduced or no immunosuppressive drug requirement in 66%, one-third of whom later relapsed to some degree with a 74 ± 7% (n= 62/79) overall survival at 5 years for SLE among the 863 HSCT procedures registered: in 2007 in the EBMT data base.
cord-005487-vac061r8	2010	We retrospectively analyzed 1257 patients (pts), 755 children (age≤18) and 502 adults, receiving fi rst single (n = 1080) or double UCBT (n = 177) in EBMT centers, between 1995 and 2009 , for malignant and non-malignant diseases, who survived at least 100 days from transplantation with neutrophils recovery and without relapse or autologous reconstitution. Prochymal® improves response rates in patients with steroid-refractory acute graft-versus-host disease involving the liver and gut: results of a randomized, placebo-controlled, multicentre phase III trial in GvHD P.J. Martin (1) , J.P. Uberti (2) Background and methods: Steroid-refractory acute GVHD (SR-GVHD) remains a signifi cant and life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). A. Nagler (1) Background: Allogeneic transplantation of hematopoietic stem cells (allo-SCT) from an HLA-matched related (MRD) or unrelated donor (URD) is a curative option for patients (pts) with high-risk hematological disease (HRHD).
cord-006273-xcw0kxjg	2009	
cord-007301-5m269nzi	2007	
cord-007626-n51v4ior	2002	
cord-007664-c5snhymz	2002	To gain an insight into the regulation of HLA in the different cell types in the CNS and to compare it to that observed in the endocrine organs, we have studied the effect of the lympho/monokines interferon (IFN)-α and -γ, tumour necrosis factor (TNF)-α, and interleukin (IL)-2 and other agents on this aspect of the biology of human fetal brain cells in culture. It has previously been reported that primary cultures of human fetal brain tissue can be a useful substrate for studying the expression of cell type-specific antigens, e.g. gangliosides, tetanus toxin receptors (Dickson et al., 1982 (Dickson et al., , 1985 , and the present data confirm that they can also be successfully employed to investigate the expression and modulation of HLA molecules.
cord-007719-3ypv9k9p	2014	Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. Thus, identifi cation of new antigenic peptides, derived from infectious agents or tumor antigens, which may bind to HLA-I or HLA-II molecules in exchange with self-peptides normally occupying the HLA-binding site ( see below), is important for developing new effective vaccines capable of activating the cellular arm of the immune responses. To reduce this complexity, one option is to group thousands of different HLA molecules into clusters of several so-called HLA supertypes: a classifi cation that refers to a group of HLA alleles with largely overlapping peptide binding specifi cities.
cord-007851-v6h1yro7	2020	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. Integrated WTS data revealed a higher priority to select promising HLA-peptides via high-resolution bioinformatics analysis, showing immune-cell-specific signatures and TCR-repertoire diversity in tumors. We then found a positive correlation between TCR diversity, reflecting clonal composition, and the expression of MHC-class І molecules, suggesting that active tumor-antigen presentation promotes the generation of antigen-specific TILs. Additionally, immune-specific signature analysis can discriminate specific immune-cell types in each patient and thus enhance the efficiency of selective HLA-peptidomic approaches. In this study, the HLA-peptidomics approach combined with comprehensive analysis of immune-specific signatures and TCR repertories showed high selectivity to determine the immunogenic T-cell epitopes. Identification of potential vaccine epitopes coupled with immune-specific signature analysis, HLA-peptidomics, and single-cell-based immunogenicity testing offers a discriminative and powerful tool for cancer-vaccine development.
cord-009323-sfxpchma	1997	
cord-009567-osstpum6	2008	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.
cord-009571-mygj2nd4	2005	
cord-009836-7o6htufh	2006	Epitope mapping performed using the Gpl 60 sequence of the patient''s autologous early HIV-1 population indicated that this response was in fact extremely focused on a single epitope encompassing Gpl60 amino acids 30-38(9), recognized in association with HLA-B44, The frequency of epitope-specific CTL was extremely high: at the earhest timepoint available for study, which may have been shghtly after the peak of the primary immune response, 1 in 1 7 peripheral blood mononuclear cells (EBMCs) were found to score as virus-specific CTL precursors by limiting dilution analysis, a technique which has recently been shown to greatly underestimate the total numher of epitope-specific T cells (55, 56) , As shown in Fig, 1 , viral variants bearing mutations in the epitopic sequence which conferred escape from recognition by epitope-specific CTL rapidly appeared in this patienc, and then increased in frequency until 164/1998 they had cotnpieteiy repiaced the transmitted virai strain.
cord-010088-s9tfvtao	2013	
cord-010092-uftc8inx	2019	Prospective testing of blood donations in endemic areas of the U.S. revealed 0.38% of donors were positive for Babesia DNA or antibodies (Moritz, NEJM, 2016) Aims: -To report results of ongoing Babesia clinical trial -To explain significance of Babesia as a TT infection Methods: In cobas â Babesia for use on the cobas â 6800/8800 Systems, is a qualitative polymerase chain reaction nucleic acid amplification test, developed to detect in whole blood (WB) donor samples the 4 Babesia species that cause human disease: B. In sensitivity analyses, there were two discrepant results for HIV testing, three for HCV, and five for anti-HBc. Summary/Conclusions: Elecsys â infectious disease parameters on the cobas e 801 analyser demonstrate high specificity/sensitivity for screening first-time blood donor samples, with similar clinical performance to other commercially available assays.
cord-010119-t1x9gknd	2017	Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip).
cord-010222-5oxie0zc	2004	
cord-013093-aa4cf44u	2020	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.
cord-013894-1bgvj62a	2019	Through cis or trans interactions with human leukocyte antigen (HLA)-G, the two most abundantly expressed inhibitory LILRs, LILRB1, and LILRB2 (LILRB1/2, also known as CD85j/d and ILT2/4), are involved in immunotolerance in pregnancy and transplantation, autoimmune diseases, and immune evasion by tumors. Structural comparisons of LILRB1/2 binding to different HLA alleles Similar to previous reports, 14,17 D1 interacts with the HLA-G1 α3 domain. As assessed by the SPR assay, dimeric HLA-G1 presenting variable peptides displayed similar binding strengths for LILRB1 and LILRB2 (with four Ig-like domains or D1D2), indicating that the peptides seem to have no effect on the interactions. Structural data in this study indicate that through trans interaction, one HLA-G1 monomer binds to one LILRB1/2 molecule. The complex structure reported here provides the first direct evidence that D1D2 is responsible for all of the interactions with HLA-Is, while D3D4 is not the reason to explain why HLA-Is that carry a single residue substitution in their α1α2 domains or in the presented peptides display variable binding affinities to LILRB2.
cord-014976-546zaoxn	2006	In order to evaluate if malignant and non malignant hematological diseases quantitatively and qualitatively affect BM derived MSCs, bone marrow from children with acute lymphoblastic leukemia (ALL diagnosis n=9, different phases of treatment n=29, end of therapy n=10), idiopathic thrombocytopenic purpura (n=16), autoimmune neutropenia (n=12) and control patients (solid tumors without BM involvement, n=30) was harvested and the mononuclear cell (MNC) fraction isolated. Case: In our hospital a total of 3 patients with relapsed Hodgkin''s disease underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling. We report a case of a young male patient of 19 years old with aggressive MS who was treated with a high-dose immunosuppressive regimen (HDIS) using myeloablation followed by autologous blood stem cell transplantation (ASCT) that has induced a dramatic and long-lasting remission of the disease.
cord-015389-vwgai4k9	2009	This study evaluates the safety of this approach, in terms of infusion-related toxicity and hematopoietic reconstitution, in 385 consecutive autologous transplantations performed from 4/97 to 9/08 in 348 patients (median age 46; underlying disease: lymphoma in 178, myeloma in 131, acute leukaemia in 17, breast cancer in 22). Patients and methods: Eight pts after allogeneic hematopoetic stem cell transplantation (HSCT) underwent MSCs infusions (median age of pts was 11 years, male/female: 6/2) between 2006 and 2009. Akiyama Tokyo Metropolitan Komagome Hospital (Tokyo, JP) Acute graft-versus-host disease (GVHD) is one of the major factors that have infl uence on the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). Material and methods: during a 8 years period we have performed 144 stem cells transplantation in 134 patients with different hematological malignancies(AML: 74; ALL: 6; CML: 7; CLL: 1, NHL: 13; Hodgkin Diseases: 16; Multiple myelomas: 24; Aplastic anaemia: 1;Myelofi brosis:1 Ewing Sarcoma: 1; Male:78 Female 66.
cord-016235-2lhrkmrv	2010	Unlike the situation with heart transplant recipients, chronic vascular rejection in lung transplants has not resulted in graft loss; however, some patients develop pulmonary hypertension particularly those with BOS [92, 111] . However, based on the link between acute rejection and development of BOS, surveillance transbronchial biopsies in asymptomatic lung transplant recipients has become common practice in many large lung transplantation centers because evidence suggests that patients who have multiple episodes of low grade (A1) lesions within the first 12 months posttransplantation develop early onset BOS. A study [49] in which surveillance transbronchial biopsies were performed at 3, 6, 9, and 12 weeks posttransplantation, at the time of symptoms, and for follow-up of acute rejection or CMV pneumonia showed that patients who develop acute small airways rejection within the first year after transplantation are at risk of development of BOS at 1.76, 3.3, and 5.5 years after detection of B3/ B4 lesion (by 1996 ISHLT criteria, see Table 7 .2), B2 lesion or B0/B1 lesion, respectively.
cord-016413-lvb79oxo	2018	Adult-onset Still''s disease (AOSD) is a rare systemic, autoinflammatory disorder that often presents in adolescence and early adulthood with fever, rash, and polyarthritis. Mutation of perforin and the MUNC13-4 genes have been seen in patients with macrophage activation syndrome (MAS), a known severe, life-threatening complication of AOSD [3] . Patients who have the chronic articular disease pattern can present with joint erosions making the differential diagnosis from RA problematic, especially in the absence of systemic signs and symptoms. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study Clinical manifestations of adult-onset Still''s disease presenting with erosive arthritis: association with low levels of ferritin and Interleukin-18
cord-016998-6n662amh	2007	
cord-017184-1ewi3dka	2008	
cord-017629-fuv157f1	2008	
cord-017702-v46ye328	2013	Deciphering the pathogen virulence factors, host susceptibility genes, and the molecular programs involved in the pathogenesis of disease has paved the way for discovery of new molecular targets for drugs, diagnostic markers, and vaccines. The pathogen genome on one hand gives us the information about the important genes conferring disease pathogenesis as well as drug resistance, while the genome of the host on the other hand will reveal the susceptibility genes, and the further knowledge of polymorphisms in genes of the host metabolic and immune system will lead to the new vaccine strategies, drugs targets, and also their treatment outcomes. Several fi eld studies have further suggested that there is a need for calibration of isoniazid dosage as per the individual tuberculosis patient''s age, acetylator status, and disease process for an effective antimicrobial outcome of drug treatment (Jeena et al.
cord-017856-4fccnygg	2018	
cord-018595-x3tleomb	2017	2. Delayed-type drug hypersensitivity: Delayed-type drug hypersensitivity reactions usually take several days to weeks following drug exposure, with variable clinical presentations that may include Maculopapular Eruption (MPE), Fixed Drug Eruption (FDE), Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Examples of strong associations of HLA alleles with specific drug-induced hypersensitivity reactions include abacavir, nevirapine, carbamazepine, and allopurinol (Table 25. [61] , who reported the weak associations of HLA-A29, B12, and MPE maculopapular drug eruption, DRESS drug reaction with eosinophilia and systemic symptoms, SJS/TEN Stevens-Johnson syndrome/toxic epidermal necrolysis DR7 in sulfonamide-related TEN, and HLA-A2, B12 in oxicam-related TEN in Europeans [61] . Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis
cord-018714-i291z2ju	2016	
cord-022474-xxy83c6u	2007	
cord-022888-dnsdg04n	2009	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.
cord-023055-ntbvmssh	2004	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.
cord-023143-fcno330z	2004	
cord-023346-8sqbqjm1	2005	• enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility.
cord-023354-f2ciho6o	2005	• enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility.
cord-023364-ut56gczm	2005	• enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility.
cord-023675-sidvbzqy	2013	
cord-028275-szb45jm2	2020	
cord-031937-qhlatg84	2020	In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 .
cord-034402-64xz1j9i	2020	This present study aims at the prediction of B cell epitopes for subunit vaccine designing against Listeria monocytogenes using a reverse vaccinology approach. For computational identification and characterization of epitopes for the preparation of subunit vaccine designing, complete proteome analysis of Listeria monocytogenes F2365 strain (GenBank accession number AE017262.2) was performed using the UniProtKB database. The first requirement in the reverse vaccinology approach of vaccine designing is to eliminate all non-allergic proteins from a complete proteome set of bacteria, Listeria monocytogenes. In this exploration and investigation, the prediction of B cell epitopes has been performed by the authors for the designing of the vaccine against listeriosis by using a reverse vaccinology approach. Tertiary structure modeling of alleles was generated with the help of HLA alleles were performed Based on low binding energy, 4 peptides were selected viz., CEETFGIRL, MKFLFPLKL, FLKIDPPIL, and VRH-HGGGHK.
cord-103662-a4ok5wqc	2020	When applied to HIV-1, Custommune predicted personalized epitopes using patient specific Human Leukocyte Antigen (HLA) alleles and viral sequences, as well as the expected HLA-peptide binding strength and potential immune escape mutations. The results allowed the identification of peptides tailored for each population and predicted to elicit both CD8+ T-cell immunity and neutralizing antibodies against structurally conserved epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To this aim, by intersecting input data from patient-specific viral sequences and HLA alleles, Custommune provides an output of epitopes of desired length filtered for their predicted specificity, immunogenicity and mutation potential. Class I and Class II HLA alleles which were predicted by Custommune to bind RBDp and RBDg epitopes of SARS-CoV-2 were used to estimate potential vaccine coverage in the populations of interest.
cord-103837-iuvigqdx	2020	
cord-104099-xhi0oxtr	2020	We defined CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. Our data present the first evidence of influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T-cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease. 10 .02.20206086 doi: medRxiv preprint immunogenicity of novel peptides in HLA-A24-expressing mice, peripheral blood of Indigenous and non-Indigenous HLA-A24 + healthy and influenza-infected individuals, and human tissues. To determine the immunogenicity of novel IAV-and IBV-derived peptides during primary and secondary influenza virus infection in vivo, we utilized HLA-A24-expressing transgenic (HHD-A24) mice 45 Table 2 ). . https://doi.org/10.1101/2020.10.02.20206086 doi: medRxiv preprint across virus strains circulating in South-East Asia and Australia suggests that the prominent HLA-A24-restricted CD8 + T-cell responses are likely to confer broad cross-reactive immunity to IAV.
cord-126015-zc7u3g34	2020	
cord-254190-bxfne94u	2015	On the contrary, humanized mice established by peripheral blood cells provide a ready platform for studying the functions of mature immune cells but the length of window appropriate for research is still limited by chronic GVHD and ongoing reduced engraftment. Distinct from their T cell companion, reconstitution of functional B lymphocytes is generally poor in humanized mice and needed to improve in the future although their primary repertoire were principally unaltered by the differences between mouse and human stromal environments [ 53 ] and their ability to produce antigen-specifi c antibody was partly developed [ 54 ] . In above three studies, investigators planted solid grafts into immunodefi cient mice before reconstitution of human immune system and induced rejection by infusion of mature human cells. Humanized immune system (HIS) mice as a tool to study human NK cell development Humanized mice as a model to study human hematopoietic stem cell transplantation
cord-255069-9xueqdri	2020	The findings suggest that homologous recombination may have occurred since its introduction into humans and be a mechanism for increased viral fitness and adaptation of SARS-CoV-2 to human populations. Evidence of viral adaptation to selective pressures as it spreads among diverse human populations has implications for the ongoing potential for changes in viral fitness over time, which in turn may impact transmissibility, disease pathogenesis and immunogenicity. Here we describe a new emerging strain of SARS-CoV-2 within the LGG clade that appears to be the result of a homologous recombination event that introduced three adjacent nucleotide changes spanning two residues of the nucleocapsid protein. Evidence for such adaptations with closely linked compensatory mutations are known to occur under host immune pressure as is well established for other adaptable RNA viruses such as HIV 1,2 and Hepatitis C virus (HCV) 3 .
cord-261392-dw56h8vj	2011	
cord-265277-ymvrserl	2020	A final round of selection on the basis of HLA 197 promiscuity (i.e., predicted binding to > 3 HLA molecules) and predicted antigenicity scoring using the 198 VaxiJen 2.0 server produced a subset of five candidate peptides (four ORF1ab, one S protein) as potential 199 targets for vaccine development (Table 1) with the hypothesis that increased HLA binding promiscuity 200 meant broader population base coverage by those peptides. As selective pressures are known to introduce viral mutations that promote fitness and can lead 266 to evasion of immune responses (59, 60), we first sought to investigate the genetic similarity of all 267 reported SARS-CoV-2 clinical isolates and identify a consensus sequence for use in our epitope 268 prediction studies. An increasing number of studies have employed predictive algorithms to identify potential HLA 285 class I epitopes for SARS-CoV-2, although relatively few have comprehensively analyzed the entire viral 286 proteome.
cord-266204-ipa017wz	2018	This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing "downstream" adaptive humoral and cellular responses to infectious pathogens and vaccines. A decade ago, we described the idea of vaccinomics and adversomics, based on the immune response network theory [5, 6] , which utilizes immunogenetics/imunogenomics and systems biology approaches to understand the basis for inter-individual variations in vaccineinduced immune responses in humans, as well as the basis for adverse side effects from vaccines [7] . Published data reveal that innate and adaptive immunity is decreased with age, but the systems-level mechanisms for these findings are unclear [66, 68] , particularly in regard to influenza and other viral vaccine responses where the morbidity, mortality, and associated healthcare costs are greater in older individuals [11] .
cord-266902-wuty839o	2012	
cord-271032-imc6woht	2020	Given the dramatic changes in various immune cell populations (Fig. 1C+D) , we next 171 assessed their composition and activation state by droplet-based scRNA-seq in 27 samples 172 from 18 COVID-19 patients (8 mild & 10 severe, cohort 1, Table S1 ) collected between day 173 3 and day 20 after symptom onset. All LDNs also expressed high levels of alarmins S100A8 and S100A9 (Fig. 5D) , whereas 343 other S100 genes (e.g. S100A4, S100A12) were strongly induced in selected neutrophil 344 Alterations of the neutrophil compartment were further interrogated by mass cytometry of 362 whole blood samples of COVID-19 patients (n=8 mild + 9 severe, cohort 1), FLI patients 363 (n=8), and age-and gender-matched controls (n=9) (Table S1), using a panel designed to 364 detect myeloid cell maturation and activation states as well as markers of 365 immunosuppression or dysfunction (Table S2) .
cord-273906-s7l0yxc0	2020	
cord-275608-joyan7ij	2012	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. 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. Box 1 | Extensive T cell cross-reactivity and apparent specificity are not incongruous From the 20 proteinogenic amino acids, it is possible to generate vast numbers of peptides of a length that can be presented by MHC molecules (see the table). First, a cross-reactive T cell repertoire generates a near perfect solution to the huge challenge of providing effective immune cover by allowing a limited number of T cells to provide immunity against virtually all foreign peptides that can bind to self MHC molecules.
cord-275677-hbv49e01	2014	Immunoliposomes loaded with the protease inhibitor indinavir and surface modified with anti-HLA-DR were found to effectively bind to HIV infected cells and deliver the antiretroviral drug leading to a significant reduction in the viral load [44] . In a recent work, lipid nanoparticles conjugated with two peptide sequences that were derived from the binding domains of CD4 designated as CD4-BP2 and CD4-BP4 were used for targeted delivery of the protease inhibitor indinavir to HIV infected CD4 + cells with high specificity [54] . The lectin actinohivin isolated from the actinomycete Longisporum albida has also been identified as an important targeting moiety that binds to the mannose residues present in the gp120 at lower concentrations with an affinity greater than anti-gp120 antibodies thereby preventing the interaction of the viral glycoprotein with CXCR4 and CCR5 chemokine receptors [13] .
cord-280172-6o1gqe8v	2020	
cord-280641-zqdrzyzl	2007	Además de investigar la posible etiología de la enfermedad, este estudio examina el situación psicosocial 15 y el curso clínico de 736 pacientes incluidos en los 6 primeros meses desde el diagnóstico histológico de sarcoidosis, y los compara con otros tantos controles pareados por edad, sexo y raza, con un seguimiento de los primeros 215 casos durante los 2 años siguientes a la inclusión 16 . Tanto la piel como los pulmones -órganos más comúnmente afectados-están siempre en contacto con estos antígenos; los estudios sobre la inmunopatogenia de la sarcoidosis apoyan que la enfermedad es el resultado de una superrespuesta inmunitaria y que hay un gran número de potenciales antígenos ambientales que pueden inducir la sensibilización y la consiguiente respuesta mediada por células responsable del desarrollo de granulomas 43 .
cord-280979-0vaarrji	2020	
cord-281141-ouno4jpl	2020	A selected pool of 11 predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. We performed T-cell activation assay using the selected 11 epitopes from the SARS-CoV-2 spike antigen in unexposed donors. As shown in Figure Multiple studies have reported pre-existing T-cell immunity in unexposed donors using spike peptide pools and attributed the response to T-cells recognizing epitopes from common coldcausing coronaviruses to which a large section of the global population is exposed (7, 8, 10) . A recent large-scale study mapped a few immunogenic regions in the SARS-CoV-2 proteome responsible for expanding many unique TCRs in a large number of convalescent COVID-19 patients and unexposed healthy donors (21) .
cord-284944-hcgfe9wv	2020	
cord-286858-zbhtl2yn	2020	
cord-286968-ud1uerc8	2020	
cord-287709-y247lan1	2014	
cord-288146-xqxznv1r	2009	
cord-288496-7rrh2gg6	2020	Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4 + and/or CD8 + T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4 + and/or CD8 + T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same.
cord-288916-i8ukefp8	2019	A pulse SILAC methodology identified IRF1, HLA-B, and ISG15 as the most dominating IFNγ inducible proteins whose synthesis was attenuated in the IFITM1/IFITM3 double-null cells. SWATH-MS proteomic screens in cells treated with IFITM1-targeted siRNA cells resulted in the attenuation of an interferon regulated protein subpopulation including MHC Class I molecules as well as IFITM3, STAT1, B2M, and ISG15. These data have implications for the function of IFITM1/3 in mediating IFNγ stimulated protein synthesis including ISG15ylation and MHC Class I production in cancer cells. The HPV16+ and IFITM1/3 positive cervical cancer cell line SiHa [38] [39] exhibit IFNγ inducible STAT1, IRF1, and IFITM1/3 proteins (Fig. 1G ). Also of note is attenuation of HLA-A, HLA-B, HLA-C, and ISG15 protein synthesis 24 h post-IFNγ treatment in the IFITM1/IFITM3 double null cells compared to parental SiHa (Fig. 5F vs 5B). By contrast, basal HLA-B protein expression was attenuated in the IFITM1/IFITM3 double null cells after IFNγ treatment (Fig. 6F vs 6E) .
cord-289711-4ab3d00h	2020	Summary Here we propose a SARS-CoV-2 vaccine design concept based on identification of highly conserved regions of the viral genome and newly acquired adaptations, both predicted to generate epitopes presented on MHC class I and II across the vast majority of the population. Here we describe an approach for prioritizing viral epitopes derived 105 from a prioritized list of 33mer peptides predicted to safely target the vulnerabilities of 106 SARS-CoV-2, generate highly immunogenic epitopes on both MHC class I and II in the 107 vast majority of the population, and maximize the likelihood that these peptides will drive 108 an adaptive memory response. Here we present a comprehensive immunogenicity map of the SARS-CoV-2 248 virus (Table S1) , and propose sixty-five 33mer peptide sequences predicted to generate 249 B and T cell epitopes from a diverse sampling of viral domains across all 10 SARS-250
cord-294212-nlekz39f	2020	
cord-296007-1gsgd22t	2020	
cord-298169-2133gahl	2020	
cord-299279-v0vznri2	2008	The peptide is deeply anchored in the B and F pockets, but with the Glu4 residue pointing away from the floor in the peptide-binding groove, making it available for interactions with a potential T-cell receptor. The overall structure of the present HLA-B*1501 peptide-binding groove is similar to the previously two determined HLA-B*1501 structures (Røder et al., 2006) and to other MHC-I molecules (see Fig. 1 ). The pGln2 peptide residue is located in the B pocket in the same orientation as the pGlu2 in the previously described HLA-B*1501-LEKARGSTY structure (Røder et al., 2006) . The pGlu4 peptide residue points away from the peptide-binding groove and the side chain does not interact with any HLA-B*1501 residues. The conformation observed does not interact with any HLA-B*1501 residues, but makes a hydrogen bond to two water molecules (HOH67 and HOH348) present between the peptide and the floor of the peptide-binding groove, thereby forming water-mediated contacts with the HLA-B*1501 protein.
cord-304635-z5vmhopa	2019	
cord-306308-zjq6cscm	2020	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.
cord-310252-0cdqhrcw	2008	
cord-312865-nno2yjae	2004	One would therefore expect that an effective vaccine should induce mucosal immunity such as that effected by secretory immunoglobulin A (IgA), which specifically prevents an infectious agent from penetrating the mucosal epithelium, and by cytotoxic T lymphocytes (CTLs), which specifically eradicate infected cells (5) . Human CTLs are specific for peptides presented in the context of human leukocyte antigen (HLA) molecules [generically known as ''''major histocompatibility complex (MHC) molecules'''']. Thus, 13 of the 15 peptides predicted to be good binders to A*0301 were found to bind to another member of the A3 supertype, HLA-A*1101. Similarly, nine of the 15 peptides predicted to be good binders to A*1101 were found to bind to HLA-A*0301 (Table 1) Once all nine supertypes have been tested, we would project to have found well over 100 different vaccine candidates. Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8(þ) cytotoxic T-cell epitopes
cord-313474-1gux1gsi	2015	Materials (or patients) and methods: We performed a multicenter, multinational, open-label, randomized study comparing anti-lymphocyte globulin (ATG-Fresenius s ) 10 mg/kg on day -3, -2 and -1 with no ATG in patients with AML (n ¼ 110) or ALL (n ¼ 45) in 1 st complete remission (CR; n ¼ 139) or 2 nd CR (n ¼ 16) who received peripheral blood stem cells from their HLA-identical sibling after standard TBI (12 Gy)/Ccclophosphamide (120 mg/kg) or busulfan (16 mg/ kg)/Cy (120 mg/kg) based myeloablative conditioning regimen. After allo-HSCT, detection of positive WT1 was followed by immunomodulatory therapeutic interventions according to the time from transplant, the presence of active graft-versus-host disease (GvHD) and the general clinical conditions: tapering and/or discontinuation of immunosuppressive drugs (IS), donor lymphocytes infusions (DLI), administration of hypomethylating agents. Introduction: Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is feasible option for patients with acute leukemia(AL)at high risk of relapse who do not have HLA-matched related or unrelated donors.
cord-316330-55nd3pwe	2020	
cord-319993-er3sm4u8	2015	
cord-320490-3jmo35jc	2020	In this study, we characterized the SARS-CoV-2 spike glycoprotein by immune-informatics techniques to put forward potential B and T cell epitopes, followed by the use of epitopes in construction of a multi-epitope peptide vaccine construct (MEPVC). Stable conformation of the MEPVC with a representative innate immune TLR3 receptor was observed involving strong hydrophobic and hydrophilic chemical interactions, along with enhanced contribution from salt-bridges towards inter-molecular stability. The study presented, herein, is an attempt to get insights about antigenic determinants of SARS-CoV-2 spike glycoprotein and highlight all antigenic epitopes [31] of the spike that can be used specifically for the design of a multi-epitope peptide vaccine construct (MEPVC) [32] to counter COVID-19 infections. The epitopes predicted by immunoinformatics techniques were fused together as well as to β-defensin adjuvant [33, 34] to boost the antibody production and longThe MEPVC affinity for an appropriate immune receptor as an agonist was checked in the step of molecular docking [60] .
cord-326554-iphe3rni	2020	This Immuno-Informatics approach leads us in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively. Nowadays epitope based vaccines provide better options in search of good treatment strategy for such type of harmful and rare malady, even if the individuals are genetically predisposed as in case of classical Whipple''s disease (Trotta et al. Immune Epitope Database (IEDB) analysis Resource tool of population coverage was used to predict population coverage of the putative epitopes that are exhibiting interaction to HLA alleles and based on MHC-II restriction data (Bui et al. PatchDock tool was deployed for interaction between selected structures of epitopes and HLA DRB1 proteins. Still no one has used vaccine based treatments for Whipple''s disease, as it is thought to be rare and possess reduced genome but considered one of the harmful pathogen of human ( Raoult et al.
cord-326983-h6gdck2u	2020	We focused on memory cells to identify epitopes that are functionally recognized during the course of SARS-CoV-2 infection and included patients with a J o u r n a l P r e -p r o o f range of symptoms to determine if any obvious associations are observed between CD8 + T cell response and disease severity. To determine the global landscape of CD8 + T cell recognition in an unbiased fashion, we built upon a genome-wide screening technology, termed T-Scan (Kula et al., 2019) , that enabled us to simultaneously screen all the memory CD8 + T cells in a patient, one HLA allele at a time, against every possible viral epitope in SARS-CoV-2, as well as the four seasonal coronaviruses that cause the common cold ( Figure 1A ).
cord-329669-z3t7plvh	2020	HLA frequencies observed were compared against two control populations: first, against published frequencies in a UK deceased donor population (n = 10,000) representing the target population of the virus, and second, using a cohort of individuals from the combined transplant waiting lists of both centres (n = 308), representing a comparator group of unaffected individuals of the same demographic. This study investigated HLA profiles of patients admitted with PCR-confirmed SARS-CoV-2 infection to identify any potential HLA bias which might indicate an impaired capacity to mount an effective immune response to the infection. All patients included in the study had previously been HLA typed to support transplantation and required hospital treatment for COVID-19 disease, indicating that their symptoms were severe, requiring clinical support or intervention. Statistical analysis was performed using MedCalc v19.3 (MedCalc Software) to compare frequencies of allele group carriage between the patient and control populations using Fisher''s exact test.
cord-329825-e9mepqvn	2020	
cord-330615-h8sktgo6	2000	Methods: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. Methods: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In preliminary immunohistochemical studies of intestinal frozen tissue sections, the pattern of staining of IELs with anti-CD56, -Pen5, -p46, -p58, and -CD94 antibodies was compared in 4 adult patients with active celiac disease and in 4 normal controls. Cytolytic T lymphocytes displaying natural killer (NK)-like activity: expression of NK-related functional receptors for HLA class I molecules (p58 and CD94) and inhibitory effect on the TCR-mediated target cell lysis or lymphokine production
cord-333391-6l0cpvgr	2020	title: SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway When we stained the cells with anticlassical HLA class I molecules (HLA-A, HLA-B, HLA-C) antibody, we recognized a significant decrease in their membrane expression when lung epithelial cells were transfected with SP1 protein (p < 0.001; Student t test) ( Figure 3D ,E). To be sure that the increase in HLA-E expression in lung epithelial cells transfected with SP1 protein is controlled by GATA3 transcription factor, we treated the cells with pyrrothiogatain. When NK cells were co-cultured with SP1-transfected Beas-2B cells, we observed an increase in the protein (p < 0.001; Student t test) ( Figure 6A ,B) and mRNA (p < 0.01; Student t test) ( Figure 6C ) expression of the inhibitory receptor NKG2A/CD94. On the contrary, lung cells, which express HLA-E molecules in the presence of SARS-CoV spike 1 protein, are able to inhibit IFN-gamma secretion and NK cell activation.
cord-333670-qv1orlv5	2020	In Italy, the possibility of performing autopsies or post-mortem diagnostic studies on suspect, probable, or confirmed COVID-19 cases has been intensively debated (5, 6) ; however, postmortem pathological analysis of COVID-19 patients in China has shown findings consistent with Acute Respiratory Distress Syndrome (ARDS) (7-9) (Figure 1 ). Consistently, recent results indicate that a systemic immune dysregulation that triggers auto-sustaining inflammatory lung damage, causing fatal respiratory-failure and consequent multiorgan-failure, is the main virus-related-death cause in patients who develop SARS-CoV-2 (10). Overall, understanding the role of pro-inflammatory cytokines certainly unravels a new battleground against the lethal clinical effect of CODIV-19 infection; this, along with the identification of a high-risk autoimmune profile, including the genotyping of Class I and II HLA, which have a key role in shaping the anti-viral immune response and Th1/Th2 lymphocyte subset response (Figure 1) , and immune-profiling, could also help to prevent these dangerous evolutions of the disease (29) .
cord-333966-st6gyozv	2015	The aim of this study was to design a high density multiepitope protein, which can be a promising multiepitope vaccine candidate against Hepatitis E virus (HEV). Therefore, the present study was undertaken to design a high density multiepitope protein compromising four HTL epitopes with high-affinity binding to the HLA molecules using the in silico analysis, and to evaluate the immunological properties of this protein in vitro. In brief, approximately 1 Â 10 5 cells/well of PBMCs of each sample in RPMI 1640 and 10% FCS were added to four wells of round-bottom 96-well plates in total volume of 180 ml/well, stimulated with 20 ml/well of truncated ORF2 protein (10 mg/ml), high density multiepitope (10 mg/ml) and Phytohemagglutinin (PHA) (5 mg/ml) (Sigma-Aldrich) separately, and incubated at 37˚C for 4 days. IFN-g ELISPOT responses to high density multiepitope protein and truncated ORF2 protein were found significantly higher in HEV-recovered individuals than control group (P < 0.001).
cord-334603-yt2pmxi3	2020	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.
cord-342942-1s32o9m8	2020	Here, we analyzed the proteolytic processing of overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes that generate antigenic peptides, aminopeptidases ERAP1, ERAP2 and IRAP. In this study, we utilized a novel approach to analyze antigen trimming by intracellular aminopeptidases ERAP1, ERAP2 and IRAP, focusing on the largest antigen of SARS-CoV-2, namely S1 spike glycoprotein. To investigate the trimming of antigenic epitope precursors by intracellular aminopeptidases that generate antigenic peptides, we used a mixture of 315 synthetic peptides derived from the sequence of the SARS-CoV-2 S1 spike glycoprotein. Our analysis of the largest antigen of SARS-CoV-2, S1 spike glycoprotein, suggests that aminopeptidase trimming can be a significant filter that helps shape which peptides will be presented by HLA.
cord-343262-zopxdw1d	2020	In this study, hAEC were isolated from full-term human placenta from 14 different donors, cryopreserved using a protocol and reagents commonly adopted for epithelial cell preservation. In anticipation that the transplant product used in any future clinical trial will be previously cryopreserved cells, the current study was undertaken to determine if there are any significant differences between the populations initially isolated from the amnion membranes, and the cells recovered following the cryopreservation procedure. The presence of CD45, a receptor linked to protein tyrosine phosphatase present in cells of the hematopoietic lineage, was detected in 9/12 of hAEC preparations immediately after isolation at an average level of 1.2% ± 1.4% cells, but greatly reduced after cryopreservation and washing steps, where only four preparations still contained an extremely low number of CD45 positive cells (0.3% ± 0.4%; p = 0.0146) ( Figure 2D ). The presence of HLA-G on hAEC after isolation was confirmed using a specific antibody, and HLA-G Amnion epithelial cells have been reported to express characteristic immunomodulatory molecules, such as HLA class Ib [21, 22] .
cord-344364-vu389d88	2020	Here, 82 individuals with COVID-19 were genotyped for HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using next-generation sequencing (NGS). Frequencies of the HLA-C*07:29, C*08:01G, B*15:27, B*40:06, DRB1*04:06, and DPB1*36:01 alleles were higher, while the frequencies of the DRB1*12:02 and DPB1*04:01 alleles were lower in COVID-19 patients than in the control population, with uncorrected statistical significance. The allele distributions of HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1 loci were compared between COVID-19 patients and control individuals. HLA-C*07:29, C*08:01G (including C*08:01 and C*08:22), B*15:27, B*40:06, DRB1*04:06, and DPB1*36:01 frequencies were higher in COVID-19 patients than in the control population, with uncorrected statistical significance (P < .05). 8 In the present study, HLA-C*07:29 was found in one COVID-19 patient, but in no individuals in the control group. 15, 16 In the present study, these SARS-susceptibility alleles were not found to occur at a significantly different frequency in COVID-19 patients after P-value correction.
cord-344691-vmc0rrrk	2004	Results: Our predictions against experimental data from four melanoma-related proteins showed that MULTIPRED ANN and HMM models could predict T-cell epitopes with high accuracy. A number of predictive methods for MHC classes I and II binding peptides are available, including those based on binding motifs (Rammensee et al., 1995) , quantitative matrices (Parker et al., 1994) , artificial neural networks (ANNs) , hidden Markov models (HMMs) (Mamitsuka, 1998) , multivariate statistical approaches (Guan et al., 2003) , support vector machines (Zhao et al., 2003) and decision trees (Savoie et al., 1999) . In our prediction of promiscuous class I T-cell epitopes, we made predictions of T-cell epitope hot spots in nucleocapsid protein of the severe acute respiratory syndrome coronavirus (SARS-CoV). MULTIPRED, a computational system developed for human leukocyte antigen (HLA) classes I-A2 and I-A3 binding, predicts individual 9-mer T-cell epitopes and also promiscuous class I regions as immunological hot spots, based on HMM and ANN models (Zhang et al., 2003) .
cord-344933-k23kzqxl	2020	Dans cette revue, nous souhaitons apporter une vue d''ensemble de la production in vitro de plaquettes à partir de cellules iPS, et de son possible potentiel transformatif, d''importance capitale dans le domaine de la transfusion des produits sanguins. De plus, contrairement aux réponses allo-immunitaires (par exemple la maladie du greffon contre l''hôte), qui sont évitables par la déplétion des leucocytes ou l''irradiation des produits dérivés du sang, être les cas réfractaires aux transfusions de plaquettes nonconcordantes pour les Antigènes des Leucocytes Humains (HLA) et des Antigènes Plaquettaires Humains (HPA) n''ont pour l''instant pas de solution [6] . La production de plaquettes ex-vivo à partir de cellules souches pluripotentes induites (iPSC) est une solution pour résoudre les problèmes liés à la transfusion allogénique. D''une part, il est possible de produire des plaquettes dérivées d''iPSC produite à partir des cellules du patient, qui dans ce cas n''éliciteront pas de réponse immunitaire. Ex vivo megakaryocyte expansion and platelet production from human cord blood stem cells
cord-346032-188gnf8j	2007	title: Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope 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. The results of the T-cell stimulation assay demonstrated that the novel N-protein peptide revealed in the present study is able to trigger specific cytotoxic T-cell response in human PBMCs. The four most immunogenic peptides (N220, N223, N227 and N317) selected in the T2-cell binding assay and the human T-cell stimulation assay were further tested for their potency in triggering immune response against the SARS N-protein expressing cells in an animal model. A peptide sequence useful for inducing the cytotoxic T-cell response should be presented as endogenous peptide epitope through proteasome digestion and have a high binding affinity towards the human MHC class I molecules.
cord-346445-hgqohdct	2020	Our findings suggest that SARS-CoV-2 mutations as well as BCG-vaccination status and a host genetic factor, HLA genotypes might affect the susceptibility to SARS-CoV-2 infection or severity of COVID-19. In this study, we comprehensively analyzed 12,343 SARS-CoV-2 genome sequences isolated from patients/ individuals in six geographic areas, including Asia, North America, South America, Europe, Oceania, and Africa, and investigated their correlations to the fatality rates in 28 different countries. In this study, we investigated the SARS-CoV-2 virus mutations and found that the frequencies of S protein 614G variant and its highly linked variant, ORF1ab 4715L, were significantly correlated with fatality rates in the 28 countries and 17 states of the United States. In summary, we comprehensively investigated SARS-CoV-2 genome mutations, BCG-vaccination status, and HLA genotypes in the 28 different countries and identified significant associations of some virus genome variants with the fatality rates.
cord-346957-bmajkabp	2009	RESULTS: First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. To investigate the capacity of candidate peptides to mobilize a human CTL repertoire, HLA-A2 + PBLs from ten HLA-A2 + donors were stimulated in vitro by DCs loaded with Alignment of the putative amino acid sequences of S proteins from eighteen SARS-CoV strains A dot among the individual sequences denoted nucleotides that are the same as the consensus. Furthermore, SARS-CoV/S-derived peptides Sp6, Sp7 and Sp8 could not only induce the increased S protein specific IFN-γ secreting T cell frequency but also the enhanced cytolytic capacity of these CTLs. To further address whether the immunogenic candidate peptide is naturally processed and presented, HLA-A2.1/ K b transgenic mice were immunized with S/pVAX1 plasmid containing a full-length cDNA encoding the SARS-CoV/S protein.
cord-347647-m9vk9m7h	2020	We recorded higher 1-year rates of graft failure (HR 2.26, 95% CI 1.17 – 4.35, p=0.01) and of 1-year overall mortality (HR 3.13, 95% CI 1.60 – 6.11, p=0.0008) after transplantation of cryopreserved compared to non-cryopreserved grafts with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match). To study the effect of cryopreserved compared to non-cryopreserved grafts, (matched-pairs) marginal Cox regression models were built and adjusted for sex, cytomegalovirus serostatus, performance score, comorbidity score, and donor-recipient ABO blood group match. The current analysis was undertaken to examine whether there are differences in survival or other transplant outcomes after transplantation of cryopreserved bone marrow or peripheral blood for severe aplastic anemia. 21 An analysis of non-cryopreserved bone marrow cellular subsets for unrelated donor transplantations failed to show an effect of graft composition on hematopoietic recovery or survival although that report included only 7 patients with aplastic anemia.
cord-347714-vxxhglx7	2020	(10, 11) The structure of the spike glycoprotein of the virus is also an extended similarity with SARS-CoV, (4) which together with COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding other proteins of the virus are candidates for vaccine development and are being explored in different settings due to the active roles of the proteins in the infectivity of the virus. (18) However studies have shown that full length spike protein vaccines for SARS-CoV may lead to antibody mediated disease enhancement causing inflammatory and liver damage in animal models (19, 20) which is why in this manuscript, we applied immuno-informatics "in silico" approaches to identify potential CD8+ cytotoxic T Cell epitopes from proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. Multi-epitope Based Peptide Vaccine Design Using Three Structural Proteins (S, E, and M) of SARS-CoV-2: An In Silico Approach
cord-348283-7xorq5ce	2020	The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Designed vaccines were then tested with different epitopes, including Truncated Ov-ASP-1 Protein (residues 10-153) and Beta defensin (45 residues long), and constructs having higher antigenicity and that are predicted to produce high antibody titers were added with the multi epitope vaccine construct to the enhance immune response (30) . For the interaction analysis of vaccine 3 and BCR (CD79), the HADDOCK server clustered 140 probable structures into 13 different clusters, which represented a total of 70% of the water-refined models.
cord-349451-vak2p7ac	2020	Studies suggest the billions of germs that compose the gut microbiota influence one''s innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. The pathogenesis of Chlamydia-related arthritis can be considered distinct from that associated with enteric bacteria since it involves metabolically active organisms residing long-term within monocytic cells in synovial tissues, after resolution of the primary genital infection and migration of the cells to the joint, a process that is known as persistence [56, [61] [62] [63] . Studies indicate inflammatory bowel disease, or, at least, intestinal inflammation, is more prevalent in SpA patients (AS or others) and some genes associated with AS are also associated with IBD [83, 85] , including genes related to gut physiology and immunology.
cord-352150-ey9kc7zj	2016	Keywords: TCR repertoire, transplantation, cross-reactivity, alloreactivity, TCR, MHC, T cell UNDeRSTANDiNG THe CROSS-ReACTiviTY Shaping the T Lymphocyte Receptor Repertoire Through evolution, numerous processes have been selected to generate a diverse repertoire of TCRαβ able to protect mammalian from pathogenic insults (Figure 1) . Despite the high diversity of the TCR repertoire, a high degree of cross-reactivity has been reported that could be explained by the "natural" ability of TCR to interact with MHC molecules (MHC focus model) as well as the interaction of TCR to a limited number of amino acids of the peptide bound to the MHC peptide groove. Cross-reactivity can be defined by the ability of a given TCR to interact with more than one pMHC complex with different presented peptides or MHC molecules. Before presenting the experimental approach aiming to quantify the number of peptides recognized by a single TCR, we would like to present clear evidences of the cross-reactivity involving memory T cells without previous antigen encounter.
cord-353877-wzndpcq3	2020	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. Consistent with global efforts, this study aims to predict potential COVID-19 Peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. The molecular docking results showed that the Spike peptide FTISVTTEI has the lowest docking energy score with the MHC I HLA-B1503 allele, hence it is predicted to have the highest binding affinity. Regarding the interaction with the MHC II molecule, the Spike peptide EVFNATRFASVYAWN showed the lowest docking energy score with the three MHC II alleles HLA-DPA1*01:03/DPB1*02:01, HLA-DQA1*01:02/DQB1*06:02, and HLA-DRB1, hence it is predicted to have the highest binding affinity to the three alleles.
cord-355374-e8k72955	2018	Influenza virus-specific CD8 + Trm in human lung tissue also maintain diverse TCR profiles-a feature important for effective T cell function and protection against the generation of viral-escape mutants [128] . HLA-I allele expression is an important predictor of cross-reactive influenza-specific CD8 + T cell immunity, with a recent study identifying five alleles (A*02:01, A*03:01, B*57:01, B*18:01, and B*08:01) capable of eliciting robust CD8 + T cell responses against immunogenic NP and M1 peptides that are conserved across all human influenza A virus, including the novel avian-derived H7N9 virus [18] . Thus, upon infection with H7N9, individuals with these HLA alleles will need time to activate and amplify new primary CD8 + T cell responses to distinct H7N9 peptide variants rather than recalling T cell responses generated against seasonal influenza viruses, potentially resulting in longer time to recovery and greater risk of severe disease compared to individuals with pre-existing cross-protective CD8 + T cell memory.