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An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8⁺ T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2−specific CD8⁺ and CD4⁺ T cells in vitro, with CD4⁺ T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8⁺ T cell epitopes, A2/S_269–277 and A2/Orf1ab_3183–3191. Using peptide−HLA tetramer enrichment, direct ex vivo assessment of A2/S₂₆₉⁺CD8⁺ and A2/Orf1ab₃₁₈₃⁺CD8⁺ populations indicated that A2/S …