CD8 + T-Cell Epitope Variations Suggest a Potential Antigen HLA-A2 Binding Deficiency for Spike Protein of SARS-CoV-2

• Published in: Frontiers in immunology Vol. 12; p. 764949
• Main Authors: Qiu, Congling, Xiao, Chanchan, Wang, Zhigang, Zhu, Guodong, Mao, Lipeng, Chen, Xiongfei, Gao, Lijuan, Deng, Jieping, Su, Jun, Su, Huanxing, Fang, Evandro Fei, Zhang, Zhang-Jin, Zhang, Jikai, Xie, Caojun, Yuan, Jun, Luo, Oscar Junhong, Huang, Li An, Wang, Pengcheng, Chen, Guobing
• Format: Journal Article
• Language: English; Norwegian
• Published: Switzerland Frontiers Media S.A 18.01.2022
• Subjects: Adult; Aged; Amino Acid Sequence; Antigen Presentation; antigen presentation deficiency; Antigenic Variation; CD8+ T-cell epitope; CD8-Positive T-Lymphocytes - immunology; COVID-19 - immunology; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; HLA-A2 Antigen - immunology; Humans; Immune Evasion; Immunology; Lymphocyte Activation; Male; Middle Aged; Molecular Docking Simulation; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; spike protein; variations; SARS-CoV-2; antigen presentation deficiency; variations; CD8+ T-cell epitope; spike protein
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.764949

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 , and those activated T cells showed cytolytic activity toward target cells. Meanwhile, n-Sp1 epitope variant significantly decreased the proportion of specific T-cell activation; n-Sp1 epitope 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.