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

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

Edité par CCSD ; PLOS -

International audience. 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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