Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease
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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, Christoph; Paschold, Lisa; Simnica, Donjete; Mohme, Malte; Willscher, Edith; von Wenserski, Lisa; Scholz, Rebekka; Wieters, Imke; Dahlke, Christine; Tolosa, Eva; Sedding, Daniel G; Ciesek, Sandra; Addo, Marylyn; Binder, Mascha.
In: IMMUNITY, Vol. 53, No. 2, 18.08.2020, p. 442-455.e4.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease
AU - Schultheiß, Christoph
AU - Paschold, Lisa
AU - Simnica, Donjete
AU - Mohme, Malte
AU - Willscher, Edith
AU - von Wenserski, Lisa
AU - Scholz, Rebekka
AU - Wieters, Imke
AU - Dahlke, Christine
AU - Tolosa, Eva
AU - Sedding, Daniel G
AU - Ciesek, Sandra
AU - Addo, Marylyn
AU - Binder, Mascha
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/8/18
Y1 - 2020/8/18
N2 - 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.
AB - 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.
U2 - 10.1016/j.immuni.2020.06.024
DO - 10.1016/j.immuni.2020.06.024
M3 - SCORING: Journal article
C2 - 32668194
VL - 53
SP - 442-455.e4
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 2
ER -