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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Veröffentlicht in:PLoS computational biology Jg. 13; H. 7; S. e1005572
Hauptverfasser: 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.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 01.07.2017
PLOS
Public Library of Science (PLoS)
Schlagworte:
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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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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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