The role of production frequency in the sharing of simian immunodeficiency virus-specific CD8+ TCRs between macaques

In some epitope-specific responses, T cells bearing identical TCRs occur in many MHC-matched individuals. The sharing of public TCRs is unexpected, given the enormous potential diversity of the TCR repertoire. We have previously studied the sharing of TCR beta-chains in the CD8(+) T cell responses to two influenza epitopes in mice. Analysis of these TCRP repertoires suggests that, even with unbiased V(D)J recombination mechanisms, some TCR beta s can be produced more frequently than others, by a process of convergent recombination. The TCR beta production frequency was shown to be a good predictor of the observed sharing of epitope-specific TCR beta s between mice. However, this study was limited to immune responses in an inbred population. In this study, we investigated TCR beta sharing in CD8(+) T cell responses specific for the immunodominant Mamu-A*01-restricted Tat-SL8/TL8 and Gag-CM9 epitopes of SIV in rhesus macaques. Multiple data sets were used, comprising a total of similar to 6000 TCR beta s sampled from 20 macaques. We observed a spectrum in the number of macaques sharing epitope-specific TCR beta s in this outbred population. This spectrum of TCR beta sharing was negatively correlated with the minimum number of nucleotide additions required to produce the sequences and strongly positively correlated with the number of observed nucleotide sequences encoding the amino acid sequences. We also found that TCR beta sharing was correlated with the number of times, and the variety of different ways, the sequences were produced in silico via random gene recombination. Thus, convergent recombination is a major determinant of the extent of TCR beta sharing.