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SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls

机译：在Covid-19和SARS的情况下，SARS-COV-2特异性T细胞免疫力和未感染的控制

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摘要

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 of ORF1) 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 Tcells showed the recognition of protein fragments that are conservedamong animal betacoronaviruses but have low homology to 'commoncold' human-associatedcoronaviruses.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.
机译：先前病原体诱导的内存T细胞可以形成易感性和随后的感染（1）的临床严重程度。关于存在于预先存在的内存T细胞的存在的存在，具有占据严重急性呼吸综合征冠状病毒2（SARS-COV-2）的潜在的存在毫无疑问。在这里，我们研究了来自Coronavirus疾病2019（Covid-19）的个体康复（Covid-19）中的SARS-COV-2的结构（核衣壳（N）蛋白）和非结构（NSP7和NSP13）的非结构（NSP7和NSP13）（n = 36 ）。在所有这些个体中，我们发现CD4和CD8 T细胞识别N蛋白的多个区域。接下来，我们表明，从SARS中恢复的患者（n = 23）（与SARS-COV感染相关的疾病）具有长期的记忆T细胞，其在SARS爆发后17年后的SARS-COV的N蛋白是反应的2003年;这些T细胞对SARS-COV-2的N蛋白显示出稳健的交叉反应性。我们还检测到没有SARS，Covid-19或与具有SARS和/或COVID-19的个体接触的人中的SARS-COV-2特异性T细胞（n = 37）。在未感染的捐赠者中的特异性T细胞具有不同的免疫致常规模式，通常靶向NSP7和NSP13以及N蛋白。 NSP7特异性TCell的表位表征表明，识别蛋白质片段，该蛋白质片段是保守的是人类贝雷伐病虫，但对“umpercold”人类相关的核病毒具有低同源性的。属，与贝替妥·韦氏病毒感染诱导结构n的多种特异性和长期的T细胞免疫力蛋白质。了解一般人群中存在的预先存在的N-和ORF1特异性T细胞如何影响SARS-COV-2感染的敏感性和发病机制对当前的Covid-19大流行来说是重要的。

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  • 来源
    《Nature》 |2020年第7821期|457-462|共6页
  • 作者

    Le Bert Nina; Tan Anthony T.; Kunasegaran Kamini; Tham Christine Y. L.; Hafezi Morteza; Chia Adeline; Chng Melissa Hui Yen; Lin Meiyin; Tan Nicole; Linster Martin; Chia Wan Ni; Chen Mark I-Cheng; Wang Lin-Fa; Ooi Eng Eong; Kalimuddin Shirin; Tambyah Paul Anantharajah; Low Jenny Guek-Hong; Tan Yee-Joo; Bertoletti Antonio;

  • 作者单位

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore|ASTAR Inst Mol & Cell Biol IMCB Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Natl Ctr Infect Dis Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore;

    Singapore Gen Hosp Dept Infect Dis Singapore Singapore;

    Natl Univ Singapore Yong Loo Lin Sch Med Dept Med Singapore Singapore|Natl Univ Singapore Hosp Univ Med Cluster Div Infect Dis Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore|Singapore Gen Hosp Dept Infect Dis Singapore Singapore;

    ASTAR Inst Mol & Cell Biol IMCB Singapore Singapore|Natl Univ Singapore Yong Loo Lin Sch Med Dept Microbiol & Immunol Singapore Singapore;

    Duke NUS Med Sch Emerging Infect Dis Program Singapore Singapore|ASTAR Singapore Immunol Network Singapore Singapore;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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