Open AccessLandscape of T‐cell repertoires with public COVID‐19‐associated T‐cell receptors in pre‐pandemic risk cohorts
Author(s) -
Simnica Donjete,
Schultheiß Christoph,
Mohme Malte,
Paschold Lisa,
Willscher Edith,
Fitzek Antonia,
Püschel Klaus,
Matschke Jakob,
Ciesek Sandra,
Sedding Daniel G,
Zhao Yu,
Gagliani Nicola,
Maringer Yacine,
Walz Juliane S,
Heide Janna,
SchulzezurWiesch Julian,
Binder Mascha
Publication year - 2021
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1340
Subject(s) - t cell receptor , immune system , pandemic , biology , covid-19 , immunology , t cell , virology , medicine , infectious disease (medical specialty) , disease
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.