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>F significantly decreased the proportion of specific T-cell activation; n-Sp1 epitope 8L>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.
【저자키워드】 SARS-CoV-2, Spike protein, variations, CD8+ T-cell epitope, antigen presentation deficiency, 【초록키워드】 immune response, pandemic, T cells, Variation, variant, peptide, in vitro, CD8, variants, binding affinity, T cell, Immune escape, T-cell, epitope, T-cell epitope, COVID-19 patients, dominant epitope, binding, convalescent COVID-19 patients, HLA-A*02:01, Analysis, antigen-presenting cell, target cells, deficiency, epitope peptide, host immune responses, T-cell activation, SARS-CoV-2 virus strain, tetramer, defined, predicted, analyzed, examined, significantly, proportion, generate, reduced, screened, characterized, contribute, the spike protein, induce, activate, activated T cell, antigen epitope, cytolytic, T2 cell, 【제목키워드】 spike, CD8, Potential,