Distinctive properties of identical twins' TCR repertoires revealed by high-throughput sequencing

Ivan V. Zvyagin, Mikhail V. Pogorelyy, Marina E. Ivanova, Ekaterina A. Komech, Mikhail Shugay, Dmitry A. Bolotin, Andrey A. Shelenkov, Alexey A. Kurnosov, Dmitriy B. Staroverov, Dmitriy M. Chudakov, Yuri B. Lebedev, Ilgar Z. Mamedov

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

Abstract

Adaptive immunity in humans is provided by hypervariable Ig-like molecules on the surface of B and T cells. The final set of these molecules in each organism is formed under the influence of two forces: individual genetic traits and the environment, which includes the diverse spectra of alien and self-antigens. Here we assess the impact of individual genetic factors on the formation of the adaptive immunity by analyzing the T-cell receptor (TCR) repertoires of three pairs of monozygous twins by next-generation sequencing. Surprisingly, we found that an overlap between the TCR repertoires of monozygous twins is similar to an overlap between the TCR repertoires of nonrelated individuals. However, the number of identical complementary determining region 3 sequences in two individuals is significantly increased for twin pairs in the fraction of highly abundant TCR molecules, which is enriched by the antigen-experienced T cells. We found that the initial recruitment of particular TCR V genes for recombination and subsequent selection in the thymus is strictly determined by individual genetic factors. J genes of TCRs are selected randomly for recombination; however, the subsequent selection in the thymus gives preference to some α but not β J segments. These findings provide a deeper insight into the mechanism of TCR repertoire generation.

Original languageEnglish
Pages (from-to)5980-5985
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number16
DOIs
Publication statusPublished - 22 Apr 2014
Externally publishedYes

Keywords

  • Immunogenetics
  • TCR repertoire analysis
  • Twin studies

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