Distinctive properties of identical twins' TCR repertoires revealed by high-throughput sequencing.
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.
Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Ivan V
IV
Zvyagin
Mikhail V
MV
Pogorelyy
Marina E
ME
Ivanova
Ekaterina A
EA
Komech
Mikhail
M
Shugay
Dmitry A
DA
Bolotin
Andrey A
AA
Shelenkov
Alexey A
AA
Kurnosov
Dmitriy B
DB
Staroverov
Dmitriy M
DM
Chudakov
Yuri B
YB
Lebedev
Ilgar Z
IZ
Mamedov
D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D015723:Gene Library; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014430:Twins, Monozygotic / Q000235:genetics*
D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell
TCR repertoire analysis; immunogenetics; twin studies