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Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires
Autoři | |
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Rok publikování | 2017 |
Druh | Článek v odborném periodiku |
Časopis / Zdroj | PLoS Computational Biology |
Fakulta / Pracoviště MU | |
Citace | |
www | http://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005572&type=printable |
Doi | http://dx.doi.org/10.1371/journal.pcbi.1005572 |
Klíčová slova | CONVERGENT RECOMBINATION; IDENTICAL-TWINS; PRENATAL ORIGIN; TCR; GENERATION; DIVERSITY; NAIVE; FREQUENCY; LEUKEMIA; IMMUNITY |
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 pre-natal life, and survive over long periods, providing the basis of the public repertoire. |