We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein_269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A^∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as “variants of concern,” was not recognized by the large CD8 T cell response seen across cohorts of HLA A^∗02⁺ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

我们通过全球最常见的 I 类人类白细胞抗原 (HLA) HLA A 研究了针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 尖峰糖蛋白_269-277表位（序列 YLQPRTFLL）的普遍细胞毒性 CD8 T 细胞反应^* 02. 迄今为止，至少在 112 个不同的 SARS-CoV-2 谱系中出现了 Spike P272L 突变，包括被归类为“关注变体”的谱系，但 HLA 队列中观察到的大量 CD8 T 细胞反应并未识别出该突变。 A ^* 02 ⁺康复期患者和个人接种了 SARS-CoV-2 疫苗，尽管这些反应包含超过 175 种不同的个体 T 细胞受体。当疫苗免疫集中于单一蛋白（例如 SARS-CoV-2 Spike）时，受高频 HLA 限制的常见 T 细胞表位的病毒逃逸可能尤其成问题，这为在下一代疫苗中包含多种病毒蛋白提供了强有力的论据，并强调需要监测新的 SARS-CoV-2 变种中的 T 细胞逃逸。