Differences in Shared T Cell receptor α Repertoire Associated with Recognition of Viral Antigens

Despite the high diversity of the αβ T cell receptor (TCR), sharing of identical TCR chains between individuals is common. This shared repertoire consists mainly of chains with few non-germline nucleotide additions. Many of these chains recognize conserved viral peptides, but it is unclear whether the number of nucleotide additions is similar regardless of specificity. We studied shared human TCR α chains associated with the recognition of viral antigens. The chains were retrieved from published databases. In sets of 6 thymus and 10 blood samples we identified these chains and analyzed their frequency and properties in the pre-immune and peripheral repertoire. For all but one virus, the identified TCR α sequences conformed to the conventional public repertoire, with a high frequency of germline rearrangements and few nucleotide additions. Surprisingly, TCR α sequences associated with Herpes simplex virus 2 (HSV-2) displayed a bimodal division, with one group of sequences having a high number of inserts, while the other group was close to germline. Our results identify a novel type of shared TCR repertoire, likely to be generated by selection instead of convergent recombination. Whether this reflects features exclusive to the immune response against HSV-2 remains to be studied.