Cellular immunity is important in determining the disease severity of COVID-19 patients. However, current understanding of SARS-CoV-2 epitopes mediating cellular immunity is limited. Here we apply T-Scan, a recently developed method, to identify CD8⁺ T cell epitopes from COVID-19 patients of four major HLA-A alleles. Several identified epitopes are conserved across human coronaviruses, which might mediate pre-existing cellular immunity to SARS-CoV-2. In addition, we identify and validate four epitopes that were mutated in the newly circulating variants, including the Delta variant. The mutations significantly reduce T cell responses to the epitope peptides in convalescent and vaccinated samples. We further determine the crystal structure of HLA-A^∗02:01/HLA-A^∗24:02 in complex with the epitope KIA_S/NYN_S, respectively, which reveals the importance of K417 and L452 of the spike protein for binding to HLA. Our data suggest that evading cellular immunity might contribute to the increased transmissibility and disease severity associated with the new SARS-CoV-2 variants.

细胞免疫对于确定 COVID-19 患者的疾病严重程度很重要。然而，目前对介导细胞免疫的 SARS-CoV-2 表位的了解有限。在这里，我们应用 T-Scan（一种最近开发的方法）来识别来自四个主要 HLA-A 等位基因的 COVID-19 患者的CD8 ⁺ T 细胞表位。几个已鉴定的表位在人类冠状病毒中是保守的，这可能介导了对 SARS-CoV-2 的预先存在的细胞免疫。此外，我们鉴定并验证了在新循环变体（包括 Delta 变体）中发生突变的四个表位。在恢复期和接种疫苗的样本中，这些突变显着降低了 T 细胞对表位肽的反应。我们进一步确定了 HLA-A ^∗ 02:01/HLA-A ^∗的晶体结构24:02 分别与表位 KIA_S/NYN_S 复合，揭示了刺突蛋白 K417 和 L452 对结合 HLA 的重要性。我们的数据表明，逃避细胞免疫可能导致与新的 SARS-CoV-2 变体相关的传染性和疾病严重程度的增加。