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PLoS Comput Biol. 2017 Jul 6;13(7):e1005572. doi: 10.1371/journal.pcbi.1005572. eCollection 2017 Jul.

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

Author information

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
2
Laboratoire de physique théorique, CNRS, UPMC and École normale supérieure, Paris, France.
3
Pirogov Russian National Research Medical University, Moscow, Russian Federation.
4
Masaryk University, Central European Institute of Technology, Brno, Czech Republic.
5
Laboratoire de physique statistique, CNRS, UPMC and École normale supérieure, Paris, France.

Abstract

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.

PMID:
28683116
PMCID:
PMC5500008
DOI:
10.1371/journal.pcbi.1005572
[Indexed for MEDLINE]
Free PMC Article

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