Private specificities of CD8 T cell responses control patterns of heterologous immunity

Kim, Sung-Kwon; Cornberg, Markus; Wang, Xiaoting Z.; Chen, Hong D.; Selin, Liisa K.; Welsh, Raymond M.

We believe that the differences in these VV-induced LCMV epitope-specific T cell responses are due to the private specificities of the TCR repertoire generated in individual mice to the different epitopes. The T cell repertoire is generated via random rearrangements of separate V, (D), and J gene segments of TCR ␣ and ␤ chains, by imprecise joining and random addition of nucleotides during this process, and by the pairing of TCR ␣ and ␤ chains. The mathematically predicted potential T cell diversity (10 15 ) is far greater than the estimate of actual diversity (2 ϫ 10 8 ) observed in mice, in part because of the limits on the total numbers of T cells (26, 27) . This gap between potential and actual diversity allows for different TCR repertoires in genetically identical hosts, and experiments have shown very little overlap of naive TCR repertoires between mice (14) . Upon immunization or infection, each host generates an antigen-specific T cell response with the best available T cell clones that randomly encounter epitope-expressing APCs. Even if each host appears to elicit comparable T cell responses with predictable immunodominance hierarchies and V␤ usage (public specificity), there lies considerable variation (private specificity) in clonal composition among the same epitope-specific T cells between individual mice (12) (13) (14) (15) .