Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires

Abstract : The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a " public " repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pre-natal life, and survive over long periods, providing the basis of the public repertoire.
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Mikhail V. Pogorelyy, Yuval Elhanati, Quentin Marcou, Anastasiia L. Sycheva, Ekaterina A. Komech, et al.. Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires. PLoS Computational Biology, Public Library of Science, 2017, 13 (7), pp.e1005572. ⟨10.1371/journal.pcbi.1005572⟩. ⟨hal-01579464⟩

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