Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease
Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease
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DOI：
10.1016/j.immuni.2020.06.024
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发表时间：
2020-08-18
期刊：
影响因子：
32.4
通讯作者：
Binder, Mascha
中科院分区：
文献类型：
--
作者：
Schultheiss, Christoph;Paschold, Lisa;Binder, Mascha
我们分析了新冠肺炎活动性感染患者或康复后患者的获得性免疫，并从这些患者的血液中创建了一个目前有1400万个B和T细胞受体(bcr和tcr)序列的资料库。B细胞反应显示IGHV3驱动的BCR簇聚在一起，与SARS-CoV-2抗体密切相关。TCR谱系的克隆性和偏斜与I型和III型干扰素应答、早期CD4(+)和CD8(+)T细胞激活以及辅助受体BTLA、TIM-3、PD-1、TIGIT和CD73的反向调节有关。TFH、Th17样细胞和非常规(但不是经典的抗病毒药物)Th1细胞极化被诱导。SARS-CoV-2特异性T细胞反应是由患者之间共享的TCR簇驱动的，具有克隆类型和病程可追溯性的特征轨迹。我们的数据提供了对SARS-CoV-2适应性免疫的基本见解，积极更新的存储库为科学界提供了迫切需要的资源，以告知治疗概念和疫苗开发。
We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR and TCR) sequences from the blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires were associated with interferon type I and III responses, early CD4(+) and CD8(+) T cell activation, and counterregulation by the co-receptors BTLA, Tim-3, PD-1, TIGIT, and CD73. Tfh, Th17-like, and nonconventional (but not classical antiviral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.