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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.