Individual variations in the murine T cell response to a specific peptide reflect variability in naive repertoires

Previous studies have analyzed the diversity of T cell responses upon immunization. Little is known, however, about the individual variability of naive repertoires and its influence on immune responses. In the present study, T cells specific for a Kd-restricted epitope derived from HLA-AS were purified from individual immunized mice using tetramers of MHC-peptide. Their TCR beta chains were sequenced revealing strong biases but large variations in BJ usage and clonal composition. Most importantly, sequence analysis from nonimmunized mice demonstrated the preexistence of a small set of splenic precursors, distinct in each mouse and comprising less than 200 cells. Therefore, differences in precursor pools appear to be the major source of individual variability in antigen-selected repertoires.