研究揭示不同人群中的新冠病毒特异性T细胞免疫
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研究揭示不同人群中的新冠病毒特异性T细胞免疫

浏览次数:    时间:2020-07-19

本期文章:《自然》:Online/在线发表

新加坡国立大学Antonio Bertoletti研究组揭示出不同人群中的新冠病毒(SARS-CoV-2)特异性T细胞免疫。2020年7月15日,《自然》在线发表了这一成果。

研究人员首先研究了在COVID-19恢复期(n=36)中SARS-CoV-2的结构性(核衣壳蛋白,NP)和非结构性(ORF1的NSP-7和NSP13)区域的T细胞应答。在所有这些研究中,研究人员证明了识别NP蛋白多个区域的CD4和CD8 T细胞的存在。然后,研究人员发现2003年爆发17年后,SARS康复患者(n=23)仍具有对SARS-NP有反应的长效记忆T细胞,并显示出与SARS-CoV-2 NP的强大交叉反应性。

出人意料的是,研究人员还频繁在没有SARS、COVID-19病史或没有与SARS/COVID-19患者接触的患者中检测到SARS-CoV-2特异性T细胞(n=37)。未感染个体中的SARS-CoV-2 T细胞表现出不同的免疫优势模式,并频繁靶向ORF-1编码的蛋白NSP7和13以及NP结构蛋白。NSP7特异性T细胞的表位表征显示与“普通感冒”人类冠状病毒具有低同源性的蛋白质片段的识别,但在动物β冠状病毒中是保守的。

因此,用β冠状病毒感染可诱导对结构蛋白NP的多特异性和持久的T细胞免疫。了解普通人群中现存的NP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理对于当前COVID-19大流行的管理至关重要。

据介绍,病原体诱导的记忆T细胞可影响后续感染的易感性和临床严重性。对于人类中是否存在识别SARS-CoV-2的记忆T细胞知之甚少。

附:英文原文

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

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

Issue&Volume: 2020-07-15

Abstract: Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections1. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

DOI: 10.1038/s41586-020-2550-z

Source: https://www.nature.com/articles/s41586-020-2550-z

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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