The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8⁺ T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8⁺ T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8⁺ T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8⁺ T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8⁺ T cell responses are detectable up to 5 months after recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8⁺ T cells during convalescence.

SARS-CoV-2引起的COVID-19大流行在全球范围内一直是一个挑战，迫切需要绘制CD8 ⁺ T细胞识别的免疫原性和免疫优势表位的概况。在这里，我们分析了来自31例COVID-19患者的样本，以识别受10个常见HLA等位基因限制的500种ILA多肽-HLA I类复合物的CD8 ⁺ T细胞识别。我们鉴定出18个CD8 ⁺ T细胞识别的SARS-CoV-2表位，包括具有源自ORF1ab且受HLA-A * 01：01限制的免疫显性特征的表位。深入表征SARS-CoV-2特异性CD8 ⁺急性重症和重症患者的T细胞反应显示NKG2A的高表达，缺乏细胞因子的产生以及基因表达谱抑制T细胞的再活化和迁移，同时维持生存。从严重和严重疾病恢复后的5个月内，可检测到SARS-CoV-2特异性CD8 ⁺ T细胞应答，这些应答在恢复期从功能障碍的效应子转变为功能性记忆CD8 ⁺ T细胞。