Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8⁺ T cells of COVID-19 patients. In total, we identified 3–8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8⁺ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8⁺ T cell immunity to SARS-CoV-2.

制定预防或治疗 2019 年冠状病毒病 (COVID-19) 的有效策略需要了解对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的自然免疫反应。我们使用公正的全基因组筛选技术来确定 SARS-CoV-2 中可被COVID-19 患者的记忆 CD8 ⁺ T 细胞识别的精确肽序列。总共，我们为 6 种最常见的人类白细胞抗原 (HLA) 类型中的每一种确定了 3-8 个表位。这些表位在患者之间广泛共享，并且位于病毒中不受突变变异影响的区域。值得注意的是，29 个共享表位中只有 3 个位于刺突蛋白中，而大多数表位位于 ORF1ab 或核衣壳蛋白中。我们还发现 CD8 ⁺ T 细胞一般不会与引起普通感冒的四种季节性冠状病毒中的表位发生交叉反应。总体而言，这些发现可以为下一代疫苗的开发提供信息，以更好地重现对 SARS-CoV-2 的自然 CD8 ⁺ T 细胞免疫。