Landscape of T-cell repertoires with public COVID-19-associated T-cell receptors in pre-pandemic risk cohorts

TY - JOUR

T1 - Landscape of T-cell repertoires with public COVID-19-associated T-cell receptors in pre-pandemic risk cohorts

AU - Simnica, Donjete

AU - Schultheiß, Christoph

AU - Mohme, Malte

AU - Paschold, Lisa

AU - Willscher, Edith

AU - Fitzek, Antonia

AU - Püschel, Klaus

AU - Matschke, Jakob

AU - Ciesek, Sandra

AU - Sedding, Daniel G

AU - Zhao, Yu

AU - Gagliani, Nicola

AU - Maringer, Yacine

AU - Walz, Juliane S

AU - Heide, Janna

AU - Schulze-Zur-Wiesch, Julian

AU - Binder, Mascha

N1 - © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

PY - 2021/8/28

Y1 - 2021/8/28

N2 - Objectives: T cells have an essential role in the antiviral defence. Public T-cell receptor (TCR) clonotypes are expanded in a substantial proportion of COVID-19 patients. We set out to exploit their potential use as read-out for COVID-19 T-cell immune responses.Methods: We searched for COVID-19-associated T-cell clones with public TCRs, as defined by identical complementarity-determining region 3 (CDR3) beta chain amino acid sequence that can be reproducibly detected in the blood of COVID-19 patients. Of the different clonotype identification algorithms used in this study, deep sequencing of brain tissue of five patients with fatal COVID-19 delivered 68 TCR clonotypes with superior representation across 140 immune repertoires of unrelated COVID-19 patients.Results: Mining of immune repertoires from subjects not previously exposed to the virus showed that these clonotypes can be found in almost 20% of pre-pandemic immune repertoires of healthy subjects, with lower representation in repertoires from risk groups like individuals above the age of 60 years or patients with cancer.Conclusion: Together, our data show that at least a proportion of the SARS-CoV-2 T-cell response is mediated by public TCRs that are present in repertoires of unexposed individuals. The lower representation of these clones in repertoires of risk groups or failure to expand such clones may contribute to more unfavorable clinical COVID-19 courses.

AB - Objectives: T cells have an essential role in the antiviral defence. Public T-cell receptor (TCR) clonotypes are expanded in a substantial proportion of COVID-19 patients. We set out to exploit their potential use as read-out for COVID-19 T-cell immune responses.Methods: We searched for COVID-19-associated T-cell clones with public TCRs, as defined by identical complementarity-determining region 3 (CDR3) beta chain amino acid sequence that can be reproducibly detected in the blood of COVID-19 patients. Of the different clonotype identification algorithms used in this study, deep sequencing of brain tissue of five patients with fatal COVID-19 delivered 68 TCR clonotypes with superior representation across 140 immune repertoires of unrelated COVID-19 patients.Results: Mining of immune repertoires from subjects not previously exposed to the virus showed that these clonotypes can be found in almost 20% of pre-pandemic immune repertoires of healthy subjects, with lower representation in repertoires from risk groups like individuals above the age of 60 years or patients with cancer.Conclusion: Together, our data show that at least a proportion of the SARS-CoV-2 T-cell response is mediated by public TCRs that are present in repertoires of unexposed individuals. The lower representation of these clones in repertoires of risk groups or failure to expand such clones may contribute to more unfavorable clinical COVID-19 courses.

UR - http://dx.doi.org/10.1002/cti2.1340

U2 - 10.1002/cti2.1340

DO - 10.1002/cti2.1340

M3 - SCORING: Journal article

C2 - 34484739

VL - 10

SP - e1340

JO - CLIN TRANSL IMMUNOL

JF - CLIN TRANSL IMMUNOL

SN - 2050-0068

IS - 9

M1 - e1340

ER -