Journal
PLOS COMPUTATIONAL BIOLOGY
Volume 13, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1005572
Keywords
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Funding
- Russian Science Foundation [15-15-00178, 14-14-00533]
- Skoltech Systems Biology Fellowship
- European Research Council [306312]
- Russian Science Foundation [15-15-00178, 17-14-00050] Funding Source: Russian Science Foundation
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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.
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