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

Autor: Pogorelyy, Mikhail V., Elhanati, Yuval, Marcou, Quentin, Sycheva, Anastasia L., Komech, Ekaterina A., Nazarov, Vadim I., Britanova, Olga V., Chudakov, Dmitriy M., Mamedov, Ilgar Z., Lebedev, Yuri B., Mora, Thierry, Walczak, Aleksandra M.
Rok vydání: 2016
Předmět:
Zdroj: PLoS Comput Biol 13(7): e1005572 (2017)
Druh dokumentu: Working Paper
DOI: 10.1371/journal.pcbi.1005572
Popis: 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.
Databáze: arXiv