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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

2020; Cell Press; Volume: 53; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2020.06.024

1097-4180

Christoph Schultheiß, Lisa Paschold, Donjetë Simnica, Malte Mohme, Edith Willscher, Lisa von Wenserski, Rebekka Scholz, Imke Wieters, Christine Dahlke, Eva Tolosa, Daniel Sedding, Sandra Ciesek, Marylyn M. Addo, Mascha Binder,

CAR-T cell therapy research

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.