Shaping the repertoire of cytotoxic T-Lymphocyte responses: Explanation for the immunodominance effect whereby cytotoxic T lymphocytes specific for immunodominant antigens prevent recognition of nondominant antigens

The immunodominance effect, whereby the presence of immunodominant epitopes prevents recognition of nondominant determinants presented on the same ant igen-presenting cell (APC) considerably restricts the repertoire of cytotox ic T lymphocyte (CTL) responses. To elucidate the molecular basis of the im munodominance effect, we compared the interactions of a dominant (B6(dom1)) and a nondominant epitope (H-Y) with their restricting class I molecule (H 2-D-b), and their ability to trigger cognate CTLs. We found that B6(dom1)/D -b complexes behaved as optimal T-cell receptor (TCR) ligands and triggered a more rapid in vivo expansion of cognate CTLs than H-Y/D-b complexes. The superiority of the dominant epitope was explained by its high cell surface density (1,012 copies/cell for B6(dom1) v10 copies/cell for H-Y) and its o ptimal affinity for cognate TCRs. Based on these results, we conclude that dominant class I-associated epitopes are those that have optimal ability to trigger TCR signals in CTLs. We propose that the rapid expansion of CTLs s pecific for dominant antigens should enable them to compete more successful ly than other CTLs for occupancy of the APC surface. (C) 1999 by The Americ an Society of Hematology.