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

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

Posted 09 Feb 2016
bioRxiv DOI: 10.1101/039297 (published DOI: 10.1371/journal.pcbi.1005572)

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 pregnancy, and survive over long periods, providing the basis of the public repertoire.

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