scholarly journals The Length Distribution of Class I–Restricted T Cell Epitopes Is Determined by Both Peptide Supply and MHC Allele–Specific Binding Preference

2016 ◽  
Vol 196 (4) ◽  
pp. 1480-1487 ◽  
Author(s):  
Thomas Trolle ◽  
Curtis P. McMurtrey ◽  
John Sidney ◽  
Wilfried Bardet ◽  
Sean C. Osborn ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Binding ◽  
Length Distribution ◽  
Class I ◽  
T Cell Epitopes ◽  
Binding Preference ◽  
Allele Specific

scholarly journals Construction and efficacy evaluation of novel swine leukocyte antigen (SLA) class I and class II allele-specific poly-T cell epitope vaccines against porcine reproductive and respiratory syndrome virus

2020 ◽  
Vol 101 (11) ◽  
pp. 1191-1201
Author(s):  
Debin Tian ◽  
Sakthivel Subramaniam ◽  
C. Lynn Heffron ◽  
Hassan M. Mahsoub ◽  
Harini Sooryanarain ◽  
...  
Keyword(s):  
T Cell ◽  
Statistical Significance ◽  
Cell Epitope ◽  
Class Ii ◽  
Class I ◽  
Respiratory Syndrome Virus ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Efficacy Evaluation ◽  
Allele Specific

Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important global swine disease. Here we report the development of subunit PRRSV-2 vaccines by expressing swine leucocyte antigen (SLA) class I and class II allele-specific epitope antigens in a robust adenovirus vector. SLA I-specific CD8 and SLA II-specific CD4 T cell epitopes of PRRSV-2 NADC20 were predicted in silico. Stable murine leukaemia cell lines (RMA-S), which are TAP-deficient and lacking endogenous class I epitope loading, were established to express different SLA I alleles. The binding stability of PRRSV T cell epitope peptides with SLA I alleles expressed on RMA-S cells was characterized. Two PRRSV poly-T cell epitope peptides were designed. NADC20-PP1 included 39 class I epitopes, consisting of 8 top-ranked epitopes specific to each of 5 SLA I alleles, and fused to 5 class II epitopes specific to SLA II alleles. NADC20-PP2, a subset of PP1, included two top-ranked class I epitopes specific to each of the five SLA I alleles. Two vaccine candidates, Ad-NADC20-PP1 and Ad-NADC20-PP2, were constructed by expressing the polytope peptides in a replication-incompetent human adenovirus 5 vector. A vaccination and challenge study in 30 piglets showed that animals vaccinated with the vaccines had numerically lower gross and histopathology lung lesions, and numerically lower PRRSV RNA loads in lung and serum after challenge compared to the controls, although there was no statistical significance. The results suggested that the Ad-NADC20-PP1 and Ad-NADC20-PP2 vaccines provided little or no protection, further highlighting the tremendous challenges faced in developing an effective subunit PRRSV-2 vaccine.

scholarly journals NetMHCpan 4.0: Improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data

2017 ◽  
Author(s):  
Vanessa Jurtz ◽  
Sinu Paul ◽  
Massimo Andreatta ◽  
Paolo Marcatili ◽  
Bjoern Peters ◽  
...  
Keyword(s):  
T Cell ◽  
Binding Affinity ◽  
Large Scale ◽  
Peptide Binding ◽  
Length Distribution ◽  
Class I ◽  
T Cell Epitopes ◽  
Data Types ◽  
Mhc Molecules ◽  
Presentation Pathway

AbstractCytotoxic T cells are of central importance in the immune system’s response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC (major histocompatibility complex) class I molecules. Peptide binding to MHC molecules is the single most selective step in the antigen presentation pathway. On the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has therefore attracted large attention.In the past, predictors of peptide-MHC interaction have in most cases been trained on binding affinity data. Recently an increasing amount of MHC presented peptides identified by mass spectrometry has been published containing information about peptide processing steps in the presentation pathway and the length distribution of naturally presented peptides. Here, we present NetMHCpan-4.0, a method trained on both binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increased predictive performance compared to state-of-the-art when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes.

T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4930-4936 ◽  
Author(s):  
Lotta Hansson ◽  
Hodjattallah Rabbani ◽  
Jan Fagerberg ◽  
Anders Österborg ◽  
Håkan Mellstedt
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Heavy Chain ◽  
T Cell Response ◽  
Class I ◽  
Type I ◽  
T Cell Epitopes ◽  
Hla Binding

Abstract The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded as a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain (VH) in MM (n = 5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype-derived peptides. A large number of human-leukocyte-antigen (HLA)–binding (class I and II) peptides were identified. The frequency of predicted epitopes depended on the database used: 245 in bioinformatics and molecular analysis section (BIMAS) and 601 in SYFPEITHI. Most of the peptides displayed a binding half-life or score in the low or intermediate affinity range. The majority of the predicted peptides were complementarity-determining region (CDR)–rather than framework region (FR)–derived (52%-60% vs 40%-48%, respectively). Most of the predicted peptides were confined to the CDR2-FR3-CDR3 “geographic” region of the Ig-VH region (70%), and significantly fewer peptides were found within the flanking (FR1-CDR1-FR2 and FR4) regions (P < .01). There were 8– to 10–amino acid (aa) long peptides corresponding to the CDRs and fitting to the actual HLA-A/B haplotypes that spontaneously recognized, albeit with a low magnitude, type I T cells (interferon γ), indicating an ongoing major histocompatibility complex (MHC) class I–restricted T-cell response. Most of those peptides had a low binding half-life (BIMAS) and a low/intermediate score (SYFPEITHI). Furthermore, 15- to 20-aa long CDR1-3–derived peptides also spontaneously recognized type I T cells, indicating the presence of MHC class II–restricted T cells as well. This study demonstrates that a large number of HLA-binding idiotypic peptides can be identified in patients with MM. Such peptides may spontaneously induce a type I MHC class I– as well as class II–restricted memory T-cell response.

Identification of SIV Nef CD8+ T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model

2014 ◽  
Vol 450 (2) ◽  
pp. 942-947 ◽  
Author(s):  
Takushi Nomura ◽  
Hiroyuki Yamamoto ◽  
Naofumi Takahashi ◽  
Taeko K. Naruse ◽  
Akinori Kimura ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Cd8 T Cell ◽  
Class I ◽  
T Cell Epitopes ◽  
Aids Model ◽  
Viral Loads ◽  
Macaque Aids Model

Synthetic peptide libraries in the determination of T cell epitopes and peptide binding specificity of class I molecules

1992 ◽  
Vol 22 (6) ◽  
pp. 1405-1412 ◽  
Author(s):  
Ton N. M. Schumacher ◽  
Grada M. Van Bleek ◽  
Marie-ThéRèSe Heemels ◽  
Karl Deres ◽  
Ka Wan Li ◽  
...  
Keyword(s):  
T Cell ◽  
Synthetic Peptide ◽  
Peptide Binding ◽  
Binding Specificity ◽  
Peptide Libraries ◽  
Class I ◽  
T Cell Epitopes ◽  
Peptide Binding Specificity

Human Cytotoxic T Cell Epitopes in HPV 11: Relationships between Allele-Specific Motifs, HLA Binding, and Stimulation in Vitro

1994 ◽  
pp. 227-232
Author(s):  
Huw Davies ◽  
Ian Tarpey ◽  
Simon Stacey ◽  
Julian Hickling ◽  
Jennifer Bartholomew ◽  
...  
Keyword(s):  
T Cell ◽  
Cytotoxic T Cell ◽  
T Cell Epitopes ◽  
Allele Specific ◽  
Hla Binding

scholarly journals Public T-cell epitopes shared among SARS-CoV-2 variants are presented on prevalent HLA class I alleles

2021 ◽  
Author(s):  
Saskia Meyer ◽  
Isaac Blaas ◽  
Ravi Chand Bollineni ◽  
Marina Delic-Sarac ◽  
Trung T Tran ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
Hla Class I ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Class I ◽  
T Cell Epitopes ◽  
Low Frequencies ◽  
Cell Responses

T-cell epitopes with broad population coverage may form the basis for a new generation of SARS-CoV-2 vaccines. However, published studies on immunoprevalence are limited by small test cohorts, low frequencies of antigen-specific cells and lack of data correlating eluted HLA ligands with T-cell responsiveness. Here, we investigate CD8 T-cell responses to 48 peptides eluted from prevalent HLA alleles, and an additional 84 predicted binders, in a large cohort of convalescents (n=83) and pre-pandemic control samples (n=19). We identify nine conserved SARS-CoV-2 specific epitopes restricted by four of the most prevalent HLA class I alleles in Caucasians, to which responding CD8 T cells are detected in 70-100% of convalescents expressing the relevant HLA allele, including two novel epitopes. We find a strong correlation between immunoprevalence and immunodominance. Using a new algorithm, we predict that a vaccine including these epitopes would induce a T cell response in 83% of Caucasians. Significance Statement: Vaccines that induce broad T-cell responses may boost immunity as protection from current vaccines against SARS-CoV-2 is waning. From a manufacturing standpoint, and to deliver the highest possible dose of the most immunogenic antigens, it is rational to limit the number of epitopes to those inducing the strongest immune responses in the highest proportion of individuals in a population. Our data show that the CD8 T cell response to SARS-CoV-2 is more focused than previously believed. We identify nine conserved SARS-CoV-2 specific CD8 T cell epitopes restricted by four of the most prevalent HLA class I alleles in Caucasians and demonstrate that seven of these are endogenously presented.

scholarly journals Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells

2019 ◽  
Vol 8 (4) ◽  
pp. e1560919 ◽  
Author(s):  
Catherine Rabu ◽  
Laurie Rangan ◽  
Laetitia Florenceau ◽  
Agnès Fortun ◽  
Maud Charpentier ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cancer Vaccines ◽  
Class Ii ◽  
Class I ◽  
T Cell Epitopes ◽  
Synthetic Long Peptides

scholarly journals HLA Class I-Restricted Cytotoxic T-Cell Epitopes of the Respiratory Syncytial Virus Fusion Protein

2000 ◽  
Vol 74 (21) ◽  
pp. 10240-10244 ◽  
Author(s):  
A. H. Brandenburg ◽  
L. de Waal ◽  
H. H. Timmerman ◽  
P. Hoogerhout ◽  
R. L. de Swart ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cytotoxic T Lymphocytes ◽  
Hla Class I ◽  
Class I ◽  
Cytotoxic T Cell ◽  
T Cell Epitopes ◽  
Cell Clones ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Virus-specific cytotoxic T lymphocytes (CTL) play a major role in the clearance of respiratory syncytial virus (RSV) infection. We have generated cytotoxic T-cell clones (TCC) from two infants who had just recovered from severe RSV infection. These TCC were functionally characterized and used to identify HLA class I (B57 and C12)-restricted CTL epitopes of RSV.

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