Publication details

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

Authors	POGORELYY M.V. ELHANATI Y. MARCOU Q. SYCHEVA A.L. KOMECH E.A. NAZAROV V.I. BRITANOVA Olga CHUDAKOV Dmitriy MAMEDOV I.Z. LEBEDEV Y.B. MORA T. WALCZAK A.M.
Year of publication	2017
Type	Article in Periodical
Magazine / Source	PLoS Computational Biology
MU Faculty or unit	Central European Institute of Technology
Citation
Web	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
Keywords	CONVERGENT RECOMBINATION; IDENTICAL-TWINS; PRENATAL ORIGIN; TCR; GENERATION; DIVERSITY; NAIVE; FREQUENCY; LEUKEMIA; IMMUNITY
Description	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.