Immunodomination results from functional differences between competing CTL

The presence of dominant epitopes suppresses generation of CTL activity tow ard other nondominant epitopes found on the same antigen-presenting cell (A PC). This phenomenon, termed immunodomination, drastically restricts the di versity of the repertoire of CTL responses. Under various experimental cond itions we assessed the in vivo expansion by tetramer staining and function by expression of O-glycans and intracellular perforin of CTL specific for a dominant (B6(dom1)) and a non-dominant (HY) H2D(b)-restricted epitope. Imm unodomination abrogated expansion rather than differentiation of HY-specifi c CTL. When immunodomination was precluded because HY was presented alone o r because high numbers of antigen-bearing APC were present, the numbers of HY-specific T cells detected after antigen priming were similar to those of B6(dom1)-specific T cells. The main difference between T cells that recogn ized B6(dom1) versus HY was functional rather than quantitative. The key fe ature of T cells specific for B6(dom1) is that they show striking up-regula tion of molecules involved in CTL effector activity rather than accumulatin g to particularly high levels, as assessed by tetramer staining. These resu lts support the emerging concept that following antigen priming, CTL popula tions of similar size can display important differences in effector functio n, and suggest that these functional differences are instrumental in shapin g the repertoire of CTL responses.