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

Significance The power of adaptive immunity in humans is realized through the hypervariable molecules: the T-cell receptors (TCRs). Each of those is built from genetically encoded parts with the addition of random nucleotides finally forming individual TCR repertoire. Despite that the individual TCR repertoire potentially can include 1011–1014 different variants, substantially less molecules are found in a single individual. The particular genetic impact on the final set of TCR molecules is still poorly understood. In this study, for the first time to the best of our knowledge, we compare deep TCR repertoires of genetically identical twins. We found that, although TCR repertoires of any pair of individuals have the same amount of identical receptors, twin repertoires share certain specific features. 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.

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