[PDF][PDF] Next-generation sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease

C Schultheiß, L Paschold, D Simnica, M Mohme… - Immunity, 2020 - cell.com
C Schultheiß, L Paschold, D Simnica, M Mohme, E Willscher, L von Wenserski, R Scholz…
Immunity, 2020cell.com
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 …
Summary
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.
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