T cell competition for the antigen-presenting cell as a model for immunodominance in the cytotoxic T lymphocyte response against minor histocompatibility antigens.

We recently demonstrated that spleen cells primed against dominant BALB.B antigens can inhibit the cytotoxic T lymphocyte (CTL) response against subdominant antigens in vitro. In this study, we show that this interference is dependent on CD8+, but not CD4+, T cells directed against dominant antigens. Similar to immunodominance in vivo, T cell interference in vitro required presentation of dominant and subdominant antigens by the same antigen-presenting cell. In vivo priming with cells expressing dominant and subdominant antigens did not induce long-lasting unresponsiveness against the latter. These results support a model in which immunodominance is mediated by T cell competition. In line with this, we found that the immunodominance effects in the CTL response against these minor histocompatibility antigens could be broken by immunization with live bone marrow-derived dendritic cells.