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

Mikhail V. Pogorelyy, Yuval Elhanati, Quentin Marcou, Anastasiia L. Sycheva, Ekaterina A. Komech, Vadim I. Nazarov, Olga V. Britanova, Dmitriy M. Chudakov, Ilgar Z. Mamedov, Yury B. Lebedev, Thierry Mora, Aleksandra M. Walczak

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Article numbere1005572
JournalPLoS Computational Biology
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 2017
Externally publishedYes

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