Pacing two T cell epitopes: A degree of randomness in the primary responseis lost upon secondary immunization

We have analyzed the hierarchy of epitope-specific T cell populations durin g a primary and a secondary CD8 T cell response. MHC-peptide tetramers were used to track the in vivo kinetics of expansion of T cell populations spec ific for two K-d-restricted epitopes simultaneously presented by a murine t umor cell following primary or recall immunizations. Individual syngeneic m ice generated remarkably different primary CTL responses, as reflected by u p to 60-fold differences in the relative contribution of each peptide-speci fic T cell population to the overall response. In these primary immunizatio ns, the CTL dominance was not dictated by the respective abundance of the p resented epitopes, In sharp contrast, the secondary response was systematic ally associated with a selective expansion of the same epitope-specific pop ulation both in vitro and in vivo. In vitro experiments indicated that the extent of expansion of each epitope-specific memory population is modulated by the epitope density. We conclude that, at least for this set of epitope s, the CTL hierarchy is not controlled by the same parameters in a primary vs a secondary response.