Immunodomination results from functional differences between competing CTL

Abstract

The presence of dominant epitopes suppresses generation of CTL activity toward other non-dominant epitopes found on the same antigen-presenting cell (APC). This phenomenon, termed immunodomination, drastically restricts the diversity of the repertoire of CTL responses. Under various experimental conditions 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 (B6dom1) and a non-dominant (HY) H2Db-restricted epitope. Immunodomination abrogated expansion rather than differentiation of HY-specific CTL. When immunodomination was precluded because HY was presented alone or 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 B6dom1-specific T cells. The main difference between T cells that recognized B6dom1 versus HY was functional rather than quantitative. The key feature of T cells specific for B6dom1 is that they show striking up-regulation of molecules involved in CTL effector activity rather than accumulating to particularly high levels, as assessed by tetramer staining. These results support the emerging concept that following antigen priming, CTL populations of similar size can display important differences in effector function, and suggest that these functional differences are instrumental in shaping the repertoire of CTL responses.