TCR β-Chain Sharing in Human CD8+ T Cell Responses to Cytomegalovirus and EBV

The CD8(+) TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCR beta chains between individuals is strongly associated with TCR beta production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCRP sequences. In this study, we analyzed a total of 2836 TCR beta sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCR beta sequences in the CD8(+) T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCR beta amino acid sequences were found to have two features that indicate efficient TCR beta production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCR beta production frequency was predictive of the extent to which both TCR beta nucleotide and amino acid sequences were shared in vivo. These results suggest that TCR beta production frequency plays an important role in the interindividual sharing of TCR beta sequences within CD8(+) T cell responses specific for CMV and EBV. The Journal of Immunology, 2008, 181: 7853-7862.