Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells

Introduction and methodsIn this present work, coronavirus subfamilies and SARS-CoV-2 Variants of Concern (VOCs) were investigated for the presence of MHC-I immunodominant viral peptides using in silico and in vitro tools.ResultsIn our results, HLA-A*02 haplotype showed the highest number of immunodo...

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Main Authors: Ágata Lopes-Ribeiro, Patrícia de Melo Oliveira, Henrique Morais Retes, Edel Figueiredo Barbosa-Stancioli, Flávio Guimarães da Fonseca, Moriya Tsuji, Jordana Grazziela Alves Coelho-dos-Reis
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语言:English
出版: Frontiers Media S.A. 2023-11-01
丛编:Frontiers in Immunology
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在线阅读:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229712/full
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author Ágata Lopes-Ribeiro
Patrícia de Melo Oliveira
Henrique Morais Retes
Edel Figueiredo Barbosa-Stancioli
Flávio Guimarães da Fonseca
Flávio Guimarães da Fonseca
Moriya Tsuji
Jordana Grazziela Alves Coelho-dos-Reis
author_facet Ágata Lopes-Ribeiro
Patrícia de Melo Oliveira
Henrique Morais Retes
Edel Figueiredo Barbosa-Stancioli
Flávio Guimarães da Fonseca
Flávio Guimarães da Fonseca
Moriya Tsuji
Jordana Grazziela Alves Coelho-dos-Reis
author_sort Ágata Lopes-Ribeiro
collection DOAJ
description Introduction and methodsIn this present work, coronavirus subfamilies and SARS-CoV-2 Variants of Concern (VOCs) were investigated for the presence of MHC-I immunodominant viral peptides using in silico and in vitro tools.ResultsIn our results, HLA-A*02 haplotype showed the highest number of immunodominant epitopes but with the lowest combined prediction score. Furthermore, a decrease in combined prediction score was observed for HLA-A*02-restricted epitopes when the original strain was compared to the VOCs, indicating that the mutations on the VOCs are promoting escape from HLA-A2-mediated antigen presentation, which characterizes a immune evasion process. Additionally, epitope signature analysis revealed major immunogenic peptide loss for structural (S) and non-structural (ORF8) proteins of VOCs in comparison to the Wuhan sequence.DiscussionThese results may indicate that the antiviral CD8+ T-cell responses generated by original strains could not be sufficient for clearance of variants in either newly or reinfection with SARS-CoV-2. In contrast, N epitopes remain the most conserved and reactive peptides across SARS-CoV-2 VOCs. Overall, our data could contribute to the rational design and development of new vaccinal platforms to induce a broad cellular CD8+ T cell antiviral response, aiming at controlling viral transmission of future SARS-CoV-2 variants.
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spelling doaj.art-2cdeea3db73c48fd89cfdb1e758f894b2023-11-03T14:01:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12297121229712Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cellsÁgata Lopes-Ribeiro0Patrícia de Melo Oliveira1Henrique Morais Retes2Edel Figueiredo Barbosa-Stancioli3Flávio Guimarães da Fonseca4Flávio Guimarães da Fonseca5Moriya Tsuji6Jordana Grazziela Alves Coelho-dos-Reis7Laboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilCentro de Tecnologia (CT) Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilAaron Diamond AIDS Research Center, Irving Medical School, Columbia University, New York, NY, United StatesLaboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilIntroduction and methodsIn this present work, coronavirus subfamilies and SARS-CoV-2 Variants of Concern (VOCs) were investigated for the presence of MHC-I immunodominant viral peptides using in silico and in vitro tools.ResultsIn our results, HLA-A*02 haplotype showed the highest number of immunodominant epitopes but with the lowest combined prediction score. Furthermore, a decrease in combined prediction score was observed for HLA-A*02-restricted epitopes when the original strain was compared to the VOCs, indicating that the mutations on the VOCs are promoting escape from HLA-A2-mediated antigen presentation, which characterizes a immune evasion process. Additionally, epitope signature analysis revealed major immunogenic peptide loss for structural (S) and non-structural (ORF8) proteins of VOCs in comparison to the Wuhan sequence.DiscussionThese results may indicate that the antiviral CD8+ T-cell responses generated by original strains could not be sufficient for clearance of variants in either newly or reinfection with SARS-CoV-2. In contrast, N epitopes remain the most conserved and reactive peptides across SARS-CoV-2 VOCs. Overall, our data could contribute to the rational design and development of new vaccinal platforms to induce a broad cellular CD8+ T cell antiviral response, aiming at controlling viral transmission of future SARS-CoV-2 variants.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229712/fullCD8+ T cellsSARS-CoV-2HLA-A2peptide microarrayimmunoinformatics
spellingShingle Ágata Lopes-Ribeiro
Patrícia de Melo Oliveira
Henrique Morais Retes
Edel Figueiredo Barbosa-Stancioli
Flávio Guimarães da Fonseca
Flávio Guimarães da Fonseca
Moriya Tsuji
Jordana Grazziela Alves Coelho-dos-Reis
Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells
Frontiers in Immunology
CD8+ T cells
SARS-CoV-2
HLA-A2
peptide microarray
immunoinformatics
title Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells
title_full Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells
title_fullStr Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells
title_full_unstemmed Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells
title_short Surveillance of SARS-CoV-2 immunogenicity: loss of immunodominant HLA-A*02-restricted epitopes that activate CD8+ T cells
title_sort surveillance of sars cov 2 immunogenicity loss of immunodominant hla a 02 restricted epitopes that activate cd8 t cells
topic CD8+ T cells
SARS-CoV-2
HLA-A2
peptide microarray
immunoinformatics
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229712/full
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