ACCUMULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES IN MAST-CELL SECRETORY GRANULES AND THEIR RELEASE UPON DEGRANULATION

To investigate the relationship between major histocompatibility compl ex (MHC) class II compartments, secretory granules, and secretory lyso somes, we analyzed the localization and fate of MHC class II molecules in mast cells. In bone marrow-derived mast cells, the bulk of MHC cla ss II molecules is contained in two distinct compartments, with featur es of both lysosomal compartments and secretory granules defined by th eir protein content and their accessibility to endocytic tracers. Type I granules display internal membrane vesicles and are accessed by exo genous molecules after a time lag of 20 min; type II granules are reac hed by the endocytic tracer later and possess a serotonin-rich electro n-dense core surrounded by a multivesicular domain. In these type I an d type II granules, MHC class II molecules, mannose-6-phosphate recept ors and lysosomal membrane proteins (lamp1 and lamp2) localize to smal l intralumenal vesicles. These 60-80-nm vesicles are released along wi th inflammatory mediators during mast cell degranulation triggered by IgE-antigen complexes. These observations emphasize the intimate conne ction between the endocytic and secretory pathways in cells of the hem atopoietic lineage which allows regulated secretion of the contents of secretory lysosomes, including membrane proteins associated with smal l vesicles.