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

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

doi:10.3389/fimmu.2023.1229712

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

Front Immunol. 2023 Nov 3:14:1229712. doi: 10.3389/fimmu.2023.1229712. eCollection 2023.

Authors

Ágata Lopes-Ribeiro¹, Patrícia de Melo Oliveira¹, Henrique Morais Retes¹, Edel Figueiredo Barbosa-Stancioli¹, Flávio Guimarães da Fonseca^{1

2}, Moriya Tsuji³, Jordana Grazziela Alves Coelho-Dos-Reis¹

Affiliations

¹ Laboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
² Centro de Tecnologia (CT) Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
³ Aaron Diamond AIDS Research Center, Irving Medical School, Columbia University, New York, NY, United States.

Abstract

Introduction and methods: In 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.

Results: In 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.

Discussion: These 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.

Keywords: CD8+ T cells; HLA-A2; SARS-CoV-2; immunoinformatics; peptide microarray.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents
CD8-Positive T-Lymphocytes*
COVID-19*
Epitopes, T-Lymphocyte / genetics
HLA-A2 Antigen
Histocompatibility Antigens Class I
Humans
Peptides
SARS-CoV-2

Substances

Epitopes, T-Lymphocyte
Histocompatibility Antigens Class I
HLA-A2 Antigen
Peptides
Antiviral Agents

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG, APQ-01499-21), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq MCTI/CNPQ/Universal 14/2014 – A Tier; process# 458134/2014-7) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). FF, EB-S, and JC-d-R received PQ fellowships from CNPq and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais (PRPq).