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Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease.
Immunity ( IF 32.4 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.immuni.2020.06.024
Christoph Schultheiß 1 , Lisa Paschold 1 , Donjete Simnica 1 , Malte Mohme 2 , Edith Willscher 1 , Lisa von Wenserski 1 , Rebekka Scholz 1 , Imke Wieters 3 , Christine Dahlke 4 , Eva Tolosa 5 , Daniel G Sedding 6 , Sandra Ciesek 7 , Marylyn Addo 4 , Mascha Binder 1
Affiliation  

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.



中文翻译:

来自COVID-19患者的T和B细胞受体库的下一代测序显示出与疾病严重程度相关的特征。

我们在患有活动性感染或康复后的COVID-19患者中描述了适应性免疫,并从这些患者的血液中创建了一个当前> 1400万个B和T细胞受体(BCR和TCR)序列的数据库。B细胞反应显示,与SARS-CoV-2抗体密切相关的IGHV3驱动的BCR聚集簇。TCR谱表的克隆性和偏斜与I型和III型干扰素反应,早期CD4 +和CD8 +有关T细胞活化,以及共受体BTLA,Tim-3,PD-1,TIGIT和CD73的反调控。Tfh,类Th17和非常规(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,这些簇在疾病过程中具有克隆型特征轨迹和可追溯性。我们的数据通过主动更新的资料库提供了对SARS-CoV-2适应性免疫的基础见解,为科学界提供了资源,为治疗概念和疫苗开发提供了急需的资源。

更新日期:2020-08-18
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