MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response

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.

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Modulation of CD8+ T Cell Response to Antigen by the Levels of Self MHC Class I

The Journal of Immunology ◽

10.4049/jimmunol.166.9.5416 ◽

2001 ◽

Vol 166 (9) ◽

pp. 5416-5421 ◽

Cited By ~ 14

Author(s):

Fabio R. Santori ◽

Ivica Arsov ◽

Stanislav Vukmanović

Keyword(s):

T Cell ◽

Mhc Class I ◽

Cell Response ◽

Cd8 T Cell ◽

T Cell Response ◽

Class I

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

10.1101/2021.10.13.463911 ◽

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.

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MHC class I-presented lung cancer-associated tumor antigens identified by immunoproteomics analysis are targets for cancer-specific T cell response

Journal of Proteomics ◽

10.1016/j.jprot.2011.02.020 ◽

2011 ◽

Vol 74 (5) ◽

pp. 728-743 ◽

Cited By ~ 15

Author(s):

Vivekananda Shetty ◽

Gomathinayagam Sinnathamby ◽

Zacharie Nickens ◽

Punit Shah ◽

Julie Hafner ◽

...

Keyword(s):

Lung Cancer ◽

T Cell ◽

Mhc Class I ◽

Cell Response ◽

Tumor Antigens ◽

T Cell Response ◽

Class I

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Dominant and cryptic antigens in the MHC class I restricted T cell response across a complex minor histocompatibility barrier: analysis and mapping by elution of cellular peptides

International Immunology ◽

10.1093/intimm/7.6.919 ◽

1995 ◽

Vol 7 (6) ◽

pp. 919-928 ◽

Cited By ~ 24

Author(s):

Elisabeth Wolpert ◽

Lars Franksson ◽

Klas Kärre

Keyword(s):

T Cell ◽

Mhc Class I ◽

Cell Response ◽

T Cell Response ◽

Class I ◽

Barrier Analysis

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An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV

Journal of General Virology ◽

10.1099/vir.0.83417-0 ◽

2008 ◽

Vol 89 (3) ◽

pp. 667-675 ◽

Cited By ~ 55

Author(s):

Efrain Guzman ◽

Geraldine Taylor ◽

Bryan Charleston ◽

Michael A. Skinner ◽

Shirley A. Ellis

Keyword(s):

T Cell ◽

Mhc Class I ◽

Cell Response ◽

Foot And Mouth Disease ◽

T Cell Response ◽

Class I ◽

Structural Proteins ◽

Infected Cattle ◽

Cell Responses ◽

Mouth Disease Virus

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hooved animals that carries enormous economic consequences. CD8+ cytotoxic T lymphocytes play an important role in protection and disease outcome in viral infections but, to date, the role of the CD8+ T-cell immune response to FMDV remains unclear. This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8+ T-cell responses to FMDV in vaccinated and in infected cattle. An in vitro assay was used to detect antigen-specific gamma interferon release by CD8+ T cells in FMDV-infected cattle of known MHC class I genotypes. A significant MHC class I-restricted CD8+ T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV. Antigen-specific MHC class I-restricted CD8+ T-cell responses were also detected in cattle vaccinated with inactivated FMDV. These responses were shown to be directed, at least in part, to epitopes within the structural proteins (P12A region) of the virus. By using mouse cells expressing single cattle MHC class I alleles, it was possible to identify the restriction elements in each case. Identification of these epitopes will facilitate the quantitative and qualitative analysis of FMDV-specific memory CD8+ T cells in cattle and help to ensure that potential vaccines induce a qualitatively appropriate CD8+ T-cell response.

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