Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease

Immunity
Christoph SchultheißMascha Binder

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 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.

Citations

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Datasets Mentioned

BETA
PRJEB38339

Methods Mentioned

BETA
flow cytometry
ELISA
immune profiling
PCA
phage display
PCR
PCRs

Key Resources (RRID) Mentioned

CVCL_0025

Software Mentioned

HighV
GraphPad
FastTreeMP
MiXCR
GraphPad Prism
FlowJo
GENOME
Archaeopteryx viewer
QUEST
SPADEVizR

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