期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：39
页码：24384-24391
DOI：10.1073/pnas.2015486117
出版社：The National Academy of Sciences of the United States of America
摘要：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/S 269 CD8 and A2/Orf1ab 3183 CD8 populations indicated that A2/S 269 CD8 T cells were detected at comparable frequencies (∼1.3 × 10 −5 ) in acute and convalescent HLA-A*02:01 patients. These frequencies were higher than those found in uninfected HLA-A*02:01 donors (∼2.5 × 10 −6 ), but low when compared to frequencies for influenza-specific (A2/M1 58 ) and Epstein–Barr virus (EBV)-specific (A2/BMLF 1280 ) (∼1.38 × 10 −4 ) populations. Phenotyping A2/S 269 CD8 T cells from COVID-19 convalescents ex vivo showed that A2/S 269 CD8 T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8 T cells expressed granzymes and/or perforin. Furthermore, the bias toward naïve, stem cell memory and central memory A2/S 269 CD8 T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8 T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8 T cell immunity in COVID-19.
关键词：CD8 T cells ; COVID-19 ; HLA-A*02:01 ; SARS-CoV-2 epitopes
