Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide “megapools,” circulating SARS-CoV-2-specific CD8⁺ and CD4⁺ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4⁺ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%–27% of the total CD4⁺ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8⁺ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4⁺ T cells in ∼40%–60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2.

了解对 SARS-CoV-2 的适应性免疫对于疫苗开发、解释 2019 年冠状病毒病 (COVID-19) 发病机制和大流行控制措施的校准非常重要。使用 HLA I 类和 II 类预测肽“巨型池”，分别在约 70% 和 100% 的 COVID-19 恢复期患者中鉴定出循环 SARS-CoV-2 特异性 CD8 ⁺和 CD4 ^{+ T 细胞。}CD4 ⁺ T 细胞对尖峰（大多数疫苗工作的主要目标）的反应是稳健的，并且与抗 SARS-CoV-2 IgG 和 IgA 滴度的大小相关。M、spike 和 N 蛋白各占总 CD4 ^{+的 11%–27%}响应，其他响应通常针对 nsp3、nsp4、ORF3a 和 ORF8 等。对于 CD8 ⁺ T 细胞，spike 和 M 被识别，至少有 8 个 SARS-CoV-2 ORF 被靶向。重要的是，我们在约 40%–60% 的未暴露个体中检测到 SARS-CoV-2 反应性 CD4 ⁺ T 细胞，这表明循环“普通感冒”冠状病毒和 SARS-CoV-2 之间存在交叉反应性 T 细胞识别。