T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.

T细胞免疫是控制病毒感染的核心。为了表征 T 细胞免疫，也为了开发疫苗，鉴定确切的病毒 T 细胞表位是基础。在这里，我们确定并表征了多个显性和次显性 SARS-CoV-2 HLA I 类和 HLA-DR 肽作为 COVID-19 恢复期和未暴露个体的潜在 T 细胞表位。SARS-CoV-2 特异性肽能够检测感染后的 T 细胞免疫，即使在血清阴性恢复期个体中也是如此。交叉反应性 SARS-CoV-2 肽揭示了 81% 未暴露个体中预先存在的 T 细胞反应，并验证了与普通感冒冠状病毒的相似性，为 SARS-CoV-2 感染中的异源免疫提供了功能基础。SARS-CoV-2 T 细胞反应的多样性与 COVID-19 的轻微症状有关，提供证据表明免疫需要识别多个表位。总之，拟议的 SARS-CoV-2 T 细胞表位能够识别异源和感染后 T 细胞免疫，并促进 COVID-19 诊断、预防和治疗措施的开发。