Secretory granules of mast cells accumulate mature and immature MHC class II molecules

Bone marrow-derived mast cells as well as dendritic cells, macrophages and B lymphocytes express major histocompatibility complex (MHC) class II molec ules. In mast cells, the majority of MHC class II molecules reside in intra cellular cell type-specific compartments, secretory granules. To understand the molecular basis for the localisation of MHC class II mole cules in secretory granules, MHC class II molecules were expressed, togethe r with the invariant chain, in the mast cell line, RBL-2H3. Using electron and confocal microscopy, we observed that in RBL-2H3 cells, mature and imma ture class II molecules accumulate in secretory granules. Two particular fe atures of class II transport accounted for this intracellular localization: first, a large fraction of newly synthesized MHC class II molecules remain ed associated with invariant chain fragments. This defect, resulting in a s lower rate of MHC class II maturation, was ascribed to a low cathepsin S ac tivity. Second, although a small fraction of class II dimers matured (i.e. became free of invariant chain), allowing their association with antigenic peptides, they were retained in secretory granules. As a consequence of thi s intracellular localization, cell surface expression of class II molecules was strongly increased by cell activation stimuli which induced the releas e of the contents of secretory granules. Our results suggest that antigen p resentation, and thereby antigen specific T cell stimulation, are regulated in mast cells by stimuli which induce mast cell activation.