Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells

Immature dendritic cells (DCs) sample their environment for antigens and af ter stimulation present peptide associated with major histocompatibility co mplex class II (MHC II) to naive T cells. We have studied the intracellular trafficking of MHC II in cultured DCs. In immature cells, the majority of MHC II was stored intracellularly at the internal vesicles of multivesicula r bodies (MVBs). in contrast, DM, an accessory molecule required for peptid e loading, was located predominantly at the limiting membrane of MVBs. Afte r stimulation, the internal vesicles carrying MHC II were transferred to th e limiting membrane of the MVB, bringing MHC II and DM to the same membrane domain. Concomitantly, the MVBs transformed into long tubular organelles t hat extended into the periphery of the cells. Vesicles that were formed at the tips of these tubules nonselectively incorporated MHC II and DM and pre sumably mediated transport to the plasma membrane. We propose that in matur ing DCs, the reorganization of MVBs is fundamental for the timing of MHC II antigen loading and transport to the plasma membrane.