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

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 abun...

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Vydané v:	PLoS computational biology Ročník 13; číslo 7; s. e1005572
Hlavní autori:	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.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 01.07.2017 PLOS Public Library of Science (PLoS)
Predmet:	Age Aging - genetics Aging - immunology Base Sequence Bioinformatics Biology and Life Sciences Cells, Cultured Cloning Cord blood Data analysis Decay rate Fetuses Gene Expression Regulation, Developmental - genetics Gene Expression Regulation, Developmental - immunology Gene Rearrangement, T-Lymphocyte - genetics Genetic Variation - genetics Humans Immune system Leukemia Life Sciences Lymphocytes Lymphocytes T Medical research Medicine and Health Sciences Molecular Sequence Data Nucleotides Pathogens Peptides Physiological aspects Receptors Receptors, Antigen, T-Cell - physiology Recombination Recombination, Genetic Research and Analysis Methods Stochastic processes Stochasticity T cell antigen receptors T cell receptors T-Cell Antigen Receptor Specificity - genetics T-cell receptor Twins Twins, Monozygotic - genetics
ISSN:	1553-7358, 1553-734X, 1553-7358
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceptualization: DMC IZM YBL TM AMW.Data curation: MVP.Formal analysis: MVP YE QM TM AMW.Funding acquisition: DMC IZM YBL TM AMW.Investigation: MVP ALS EAK OVB.Methodology: MVP YE QM TM AMW.Project administration: DMC IZM YBL TM AMW.Resources: MVP ALS EAK OVB.Software: MVP YE QM VIN.Supervision: DMC IZM YBL TM AMW.Writing – original draft: TM AMW MVP.Writing – review & editing: TM AMW MVP. The authors have declared that no competing interests exist.
ISSN:	1553-7358 1553-734X 1553-7358
DOI:	10.1371/journal.pcbi.1005572