SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
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DOI：
10.1038/s41586-020-2550-z
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发表时间：
2020-07-15
期刊：
影响因子：
64.8
通讯作者：
Bertoletti, Antonio
中科院分区：
文献类型：
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作者：
Le Bert, Nina;Tan, Anthony T.;Bertoletti, Antonio
在从SARS或COVID-19中康复的个体和未暴露的供体中发现了SARS-CoV-2反应性T细胞，尽管具有不同的免疫反应性模式。由先前病原体诱导的记忆T细胞可以形成对后续感染的易感性和临床严重性（1）。人类中存在的记忆T细胞具有识别严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的潜力，对此知之甚少。在这里，我们研究了从2019年冠状病毒病（COVID-19）中康复的个体（n = 36）对SARS-CoV-2的结构（核衣壳（N）蛋白）和非结构（ORF 1的NSP 7和NSP 13）区域的T细胞应答。在所有这些个体中，我们发现CD 4和CD 8 T细胞识别N蛋白的多个区域。接下来，我们发现从SARS（与SARS-CoV感染相关的疾病）中康复的患者（n = 23）在2003年SARS爆发后17年拥有对SARS-CoV N蛋白具有反应性的持久记忆T细胞;这些T细胞对SARS-CoV-2的N蛋白表现出强烈的交叉反应性。我们还在没有SARS、COVID-19病史或与SARS和/或COVID-19患者接触的个体中检测到SARS-CoV-2特异性T细胞（n = 37）。在未感染的供体中，SARS-CoV-2特异性T细胞表现出不同的免疫优势模式，并且经常靶向NSP 7和NSP 13以及N蛋白。NSP 7特异性T细胞的表位表征显示了对动物β冠状病毒中保守但与“普通感冒”人类相关冠状病毒同源性低的蛋白片段的识别。因此，β冠状病毒感染诱导针对结构N蛋白的多特异性和持久的T细胞免疫。了解存在于普通人群中的预先存在的N-和ORF 1-特异性T细胞如何影响SARS-CoV-2感染的易感性和发病机制，对于当前COVID-19大流行的管理非常重要。
SARS-CoV-2-reactive T cells were found in individuals who had recovered from SARS or COVID-19 and in unexposed donors, although with different patterns of immunoreactivity.Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections(1). Little is known about the presence in humans of pre-existing memory T cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 ofORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36). In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2. We also detected SARS-CoV-2-specific T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specific T cells in uninfected donors exhibited a different pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein. Epitope characterization of NSP7-specific T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to 'common cold' human-associated coronaviruses. Thus, infection with betacoronaviruses induces multi-specific and long-lasting T cell immunity against the structural N protein. Understanding how pre-existing N- and ORF1-specific T cells that are present in the general population affect the susceptibility to and pathogenesis of SARS-CoV-2 infection is important for the management of the current COVID-19 pandemic.