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.

Studies of the T cell receptor repertoire directed against viral epitopes have revealed three principles. First, the repertoire is highly diverse, with sometimes hundreds of distinct clones directed against a single epitope (10) (11) (12) . Second, epitope-specific responses between individuals are often dominated by distinct V ␤ TCR usage and conserved amino acid motifs in the TCR CDR3 region, which recognizes the peptide-MHC (public specificities; references 11, 13, 14) . Third, genetically identical hosts nevertheless have distinct epitope-specific T cell populations with different amino acid sequences in the CDR3 regions (private specificities; refer-ences 10, 15, 16) . We questioned here whether "private" determinants, which may not be very important for the recognition of the epitope initially driving that particular T cell, may be important in a cross-reactive recognition of another epitope. This would mean that some individuals experiencing infections in sequence with two viruses may generate cross-reactive responses between the viruses, whereas other individuals with similar MHC would not. This variability could presumably influence viral clearance and immunopathology. Here, we show that the LCMV epitope-specific T cell responses elicited by VV infection are indeed a function of the unique T cell responses of an individual host. Some common patterns are seen, but the private specificities of LCMV-immune T cell populations drive this cross-reactive antigen recognition.