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下一代测序揭示与COVID-19疾病严重程度相关的特征
作者:小柯机器人 发布时间:2020/7/3 13:21:46

德国哈勒-维腾贝格大学Mascha Binder研究小组通过对COVID-19患者的T和B细胞受体库的下一代测序,发现了与疾病严重程度相关的特征。相关论文于2020年6月29日在线发表于《免疫》。

研究人员在感染或康复后的COVID-19患者中检测了适应性免疫,并从这些患者的血液中创建了超过 1400万个B和T细胞受体(BCR,TCR)序列的存储库。B细胞反应显示,与SARS-CoV-2抗体紧密相关的IGHV3驱动的BCR簇。TCR库的克隆性和偏离与干扰素I和III型应答、早期CD4+和CD8+T细胞活化以及共受体BTLA、Tim-3、PD-1、TIGIT和CD73的反调节有关。Tfh、Th17样和非经典(但不是经典的抗病毒)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,这在疾病过程中具有克隆型特征轨迹和可追溯性。这些数据提供了对SARS-CoV-2适应性免疫的基础性了解,为治疗理念和疫苗开发提供了资源。
 
附:英文原文

Title: Next Generation Sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease

Author: Christoph Schulthei, Lisa Paschold, Donjete Simnica, Malte Mohme, Edith Willscher, Lisa von Wenserski, Rebekka Scholz, Imke Wieters, Christine Dahlke, Eva Tolosa, Daniel G. Sedding, Sandra Ciesek, Marylyn Addo, Mascha Binder

Issue&Volume: 2020-06-29

Abstract: 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, TCR) sequences from 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 was associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation and counterregulation by the coreceptors BTLA, Tim-3, PD-1, TIGIT and CD73. Tfh, Th17-like and nonconventional (but not classical anti-viral) 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.

DOI: 10.1016/j.immuni.2020.06.024

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30279-X

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx