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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

: Schultheiß, C.; Paschold, L.; Simnica, D.; Mohme, M.; Willscher, E.; Wenserski, L. von; Scholz, R.; Wieters, I.; Dahlke, C.; Tolosa, E.; Sedding, D.G.; Ciesek, S.; Addo, M.; Binder, M.


Immunity 53 (2020), No.2, pp.442-455.e4
ISSN: 1074-7613
ISSN: 1097-4180
Journal Article
Fraunhofer IME ()

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.