Immunization with dendritic cells breaks immunodominance in CTL responses against minor histocompatibility and synthetic peptide antigens

We have examined the mechanisms involved in immunodominance in two differen t experimental models: the cytotoxic T lymphocyte (CTL) response in B6 mice against minor histocompatibility antigens of BALB.B mice, and the response of B6 mice against a mixture of five synthetic peptides corresponding to w ell-defined immunogenic epitopes, The CTL responses in these models focus o n a few dominant epitopes, whereas no or only weak responses can be detecte d against other subdominant epitopes, Neither of these immunodominance phen omena can be explained by insufficient presentation of subdominant epitopes in the presence of the dominant ones. Immunodominance could also be demons trated in an in vitro system, in which B6 splenocytes primed with BALB.B co uld interfere with the CTL response against subdominant antigens, This inte rference Tvas dependent on CD8(+) T cells and on the simultaneous presentat ion of dominant and subdominant antigens on the same antigen-presenting cel l, suggesting T cell competition around the antigen-presenting cell as a po tential explanation. The immunodominance in both systems could be broken by immunization with dendritic cells (from BALB.B or from B6 loaded with pept ides), This procedure allowed detection of CTL responses against both domin ant and previously subdominant antigens.