Broad and strong memory CD4+and CD8+T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19
Broad and strong memory CD4+and CD8+T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19
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DOI：
10.1101/2020.06.05.134551
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发表时间：
2020-09-04
影响因子：
30.5
通讯作者：
Dong, Tao
中科院分区：
文献类型：
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作者：
Peng, Yanchun;Mentzer, Alexander J.;Dong, Tao
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗和治疗方法的开发将取决于对病毒免疫的理解。我们研究了42名从COVID-19中恢复的患者（28名轻度疾病，14名重度疾病）和16名未暴露的供体的T细胞记忆，使用基于干扰素-γ的测定方法，使用SARS-CoV-2（ORF 1除外）的肽。与轻度病例相比，重度病例的T细胞反应的广度和幅度显著更高。总的和加标特异性T细胞应答与加标特异性抗体应答相关。我们鉴定了41种含有CD 4（+）和/或CD 8（+）表位的肽，包括6个免疫显性区域。确定了6个优化的CD 8（+）表位，肽-MHC五聚体阳性细胞显示中枢和效应记忆表型。在轻度病例中，观察到较高比例的SARS-CoV-2特异性CD 8（+）T细胞。与较轻疾病相关的T细胞应答的鉴定将支持对保护性免疫的理解，并突出了在未来的COVID-19疫苗设计中包括非刺突蛋白的潜力。对于患有严重COVID-19疾病的患者是否可以产生针对SARS-CoV-2的T细胞应答，已经产生了疑问。陶东及其同事报告说，COVID-19康复期患者体内存在功能性记忆CD 4（+）和CD 8（+）T细胞，这些细胞识别跨越病毒蛋白质组的多个表位。CD 4（+）T细胞在严重疾病患者的记忆反应中占主导地位，而在轻度疾病患者中发现较高比例的CD 8（+）T细胞。
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-gamma-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4(+)and/or CD8(+)epitopes, including six immunodominant regions. Six optimized CD8(+)epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8(+)T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4(+)and CD8(+)T cells that recognize multiple epitopes that span the viral proteome. CD4(+)T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8(+)T cells were found in patients with mild disease.