RT Journal Article
SR Electronic
T1 Two types of human TCR differentially regulate reactivity to self and non-self antigens
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.27.489747
DO 10.1101/2022.04.27.489747
A1 Assya Trofimov
A1 Philippe Brouillard
A1 Jean-David Larouche
A1 Jonathan Séguin
A1 Jean-Philippe Laverdure
A1 Ann Brasey
A1 Gregory Ehx
A1 Denis-Claude Roy
A1 Lambert Busque
A1 Silvy Lachance
A1 Sébastien Lemieux
A1 Claude Perreault
YR 2022
UL http://biorxiv.org/content/early/2022/04/28/2022.04.27.489747.abstract
AB Based on analyses of TCR sequences from over 1,000 individuals, we report that the TCR repertoire is composed of two ontogenically and functionally distinct types of TCRs. Their production is regulated by variations in thymic output and terminal deoxynucleotidyl transferase (TDT) activity. Neonatal TCRs derived from TDT-negative progenitors persist throughout life, are highly shared among subjects, and are polyreactive to self and microbial antigens. Thus, >50% of cord blood TCRs are responsive to SARS-CoV2 and other common pathogens. TDT- dependent TCRs present distinct structural features and are less shared among subjects. TDT- dependent TCRs are produced in maximal numbers during infancy when thymic output and TDT activity reach a summit, are more abundant in subjects with AIRE mutations, and seem to play a dominant role in graft-versus-host disease. Factors decreasing thymic output (age, male sex) negatively impact TCR diversity. Males compensate for their lower repertoire diversity via hyperexpansion of selected TCR clonotypes.Competing Interest StatementThe authors have declared no competing interest.