Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals
Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals
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DOI：
10.1016/j.cell.2020.05.015
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发表时间：
2020-06-25
期刊：
影响因子：
64.5
通讯作者：
Sette, Alessandro
中科院分区：
文献类型：
--
作者：
Grifoni, Alba;Weiskopf, Daniela;Sette, Alessandro
了解SARS-CoV-2的适应性免疫对于疫苗开发、解释2019冠状病毒病（COVID-19）的发病机制以及校准大流行控制措施非常重要。使用HLA I类和II类预测肽“megapools”，分别在70%和100%的COVID-19康复期患者中鉴定出循环SARS-CoV-2特异性CD 8（+）和CD 4（+）T细胞。CD 4（+）T细胞对刺突（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和伊加滴度的大小相关。M、spike和N蛋白各占总CD 4（+）应答的11%-27%，另外的应答通常靶向nsp 3、nsp 4、ORF 3a和ORF 8等。对于CD 8（+）T细胞，识别spike和M，靶向至少8个SARS-CoV-2 ORF。重要的是，我们在40%-60%的未暴露个体中检测到SARS-CoV-2反应性CD 4（+）T细胞，这表明循环的“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。
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 similar to 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 antiSARS-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 similar to 40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating "common cold" coronaviruses and SARS-CoV-2.