EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES IN HELA-CELLS PROMOTES THE RECRUITMENT OF AP-1 GOLGI-SPECIFIC ASSEMBLY PROTEINS ON GOLGI MEMBRANES

The newly synthesized major histocompatibility complex (MHC) class II molecules, an alpha beta dimer associated with the Ii invariant chain, must be targeted to endosomal, lysosomal enzyme-rich compartments in order to bind and present immunogenic peptides, The precise route foll owed by this complex at the exit of the trans Golgi network, the last sorting station of the biosynthetic pathway, is poorly understood, We show here that overexpression of alpha beta Ii complexes in HeLa cells promotes the first step of clathrin-coat assembly in vitro, that is t he ARF-dependent translocation of AP-1 Golgi-specific assembly protein s on membranes, In contrast, alpha beta dimers alone or associated wit h Ii lacking most of its cytoplasmic domain fail to recruit AP-1, This study strongly suggests that the invariant chain (Ii) is responsible for the AP-l-dependent sorting of the alpha beta dimers in the trans-G olgi network of HeLa cells and that the MHC class II molecules are, li ke the mannose 6-phosphate receptors, transported directly from this c ompartment to endosomes via clathrin-coated vesicles.