Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals.

Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals.
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DOI:
10.1038/s41421-021-00321-x
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发表时间:
2021-09-28
期刊:
影响因子:
33.5
通讯作者:
Wang F
Wang F
中科院分区:
生物学1区
文献类型:
--
作者:
Luo L;Liang W;Pang J;Xu G;Chen Y;Guo X;Wang X;Zhao Y;Lai Y;Liu Y;Li B;Su B;Zhang S;Baniyash M;Shen L;Chen L;Ling Y;Wang Y;Liang Q;Lu H;Zhang Z;Wang F

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SARS-CoV-2爆发已被世界卫生组织宣布为全球大流行。然而,关于抗原特异性T细胞介导的对SARS-CoV-2感染的免疫应答还有许多未知数。在这里,我们提出了单细胞TCR-seq和RNA-seq,以分析从最近出院的COVID-19患者中收集的血液T细胞的TCR库和免疫代谢功能的动态。我们发现,虽然出院患者TCR库的多样性增加,但在无病毒后约1周恢复到基础水平。T细胞库的动态与基因特征从抗病毒反应到代谢适应的深刻转变相关。我们还证明了最高扩增的T细胞克隆(约占总T细胞的10%)在CD 8 + T细胞中显示出关键的抗病毒特征,证实了抗原特异性T细胞在对抗SARS-CoV-2中的关键作用。我们的工作为进一步分析COVID-19患者的适应性免疫提供了基础,也对开发基于T细胞的SARS-CoV-2疫苗具有意义。
SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8+ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.
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