美国La Jolla免疫学研究所Alessandro Sette研究团队揭示新冠病毒（SARS-CoV-2）患者体内的T细胞响应靶点。这一研究成果于2020年5月14日在线发表在《细胞》上。

使用HLA I和II类预测肽库，研究人员分别在约70％和100％的COVID-19康复患者中鉴定出SARS-CoV-2特异性循环CD8⁺和CD4⁺T细胞。CD4⁺T细胞对突刺蛋白的反应是大多数疫苗研究的主要目标，这些反应强烈且与抗SARS-CoV-2 IgG和IgA滴度的大小相关。 M蛋白、刺突蛋白和N蛋白各自占总CD4⁺应答的11-27％，其他应答通常针对nsp3、nsp4、ORF3a和ORF8等。对于CD8⁺T细胞，可识别出刺突和M，且至少靶向8个SARS-CoV-2的ORF。

重要的是，研究人员在约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T细胞识别对“普通感冒”冠状病毒与SARS-CoV-2之间具有交叉反应。

据悉，了解SARS-CoV-2的适应性免疫对于疫苗开发、阐明2019冠状病毒病（COVID-19）发病机理以及改进大流行的控制措施都至关重要。

附：英文原文

Title: Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

Author: Alba Grifoni, Daniela Weiskopf, Sydney I. Ramirez, Jose Mateus, Jennifer M. Dan, Carolyn Rydyznski Moderbacher, Stephen A. Rawlings, Aaron Sutherland, Lakshmanane Premkumar, Ramesh S. Jadi, Daniel Marrama, Aravinda M. de Silva, April Frazier, Aaron Carlin, Jason A. Greenbaum, Bjoern Peters, Florian Krammer, Davey M. Smith, Shane Crotty, Alessandro Sette

Issue&Volume: 2020-05-14

Abstract: 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-2specific 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-2reactive CD4+ T cells in ～40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.

DOI: 10.1016/j.cell.2020.05.015

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3