Tumor cells present MHC class II-restricted nuclear and mitochondrial antigens and are the predominant antigen presenting cells in vivo

MHC class II-restricted tumor Ags presented by class II+ tumor cells identi fied to date are derived from proteins expressed in the cytoplasm or plasma membrane of tumor cells. It is unclear whether MMC class II+ tumor cells p resent class II-restricted epitopes derived from other intracellular compar tments, such as nuclei and/or mitochondria, and whether class II+ tumor cel ls directly present Ag in vivo. To address these questions, a model Ag, hen egg lysozyme, was targeted to various subcellular compartments of mouse sa rcoma cells, and the resulting cells were tested for presentation of three lysozyme epitopes in vitro and for presentation of nuclear Ag in vivo, In i n vitro studies, Ags localized to all tested compartments (nuclei, cytoplas m, mitochondria, and endoplasmic reticulum) are presented in the absence in variant chain and H-2M, Coexpression of invariant chain and H-2M inhibit pr esentation of some, but not all, of the epitopes, In vivo studies demonstra te that class II+ tumor cells, and not host-derived cells, are the predomin ant APC for class II-restricted nuclear Ags, Because class II+ tumor cells are effective APC in vivo and probably present novel tumor Ag epitopes not presented by host-derived APC, their inclusion in cancer vaccines may enhan ce activation of tumor-reactive CD4(+) T cells.