In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-18)
Abstract:
We identified SARS-CoV-2 specific antigen epitopes by HLA-A2 binding affinity analysis and characterized their ability to activate T cells. As the pandemic continues, variations in SARS-CoV-2 virus strains have been found in many countries. In this study, we directly assess the immune response to SARS-CoV-2 epitope variants. We first predicted potential HLA-A*02:01-restricted CD8 + T-cell epitopes of SARS-CoV-2. Using the T2 cell model, HLA-A*02:01-restricted T-cell epitopes were screened for their binding affinity and ability to activate T cells. Subsequently, we examined the identified epitope variations and analyzed their impact on immune response. Here, we identified specific HLA-A2-restricted T-cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides were confirmed to bind with HLA-A*02:01 and potentially be presented by antigen-presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8 + T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. These epitopes could activate and generate epitope-specific T cells in vitro , and those activated T cells showed cytolytic activity toward target cells. Meanwhile, n-Sp1 epitope variant 5L & gt;F significantly decreased the proportion of specific T-cell activation; n-Sp1 epitope 8L & gt;V variant showed significantly reduced binding to HLA-A*02:01 and decreased proportion of n-Sp1-specific CD8 + T cell, which potentially contributes to the immune escape of SARS-CoV-2. Our data indicate that the variation of a dominant epitope will cause the deficiency of HLA-A*02:01 binding and T-cell activation, which subsequently requires the formation of a new CD8 + T-cell immune response in COVID-19 patients.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.764949
DOI:
10.3389/fimmu.2021.764949.s001
DOI:
10.3389/fimmu.2021.764949.s002
DOI:
10.3389/fimmu.2021.764949.s003
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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