MHC CLASS-II TRANSPORT FROM LYSOSOMAL COMPARTMENTS TO THE CELL-SURFACE IS DETERMINED BY STABLE PEPTIDE BINDING, BUT NOT BY THE CYTOSOLIC DOMAINS OF THE ALPHA-CHAINS AND BETA-CHAINS

Inside APCs, MHC class II molecules associate with antigenic peptides before reaching the cell surface. This association takes place in comp artments of the endocytic pathway, more related to endosomes or lysoso mes depending on the cell type, Here, we compared MHC class II transpo rt from endosomal vs lysosomal compartments to the plasma membrane. We show that transport of MHC class II molecules to the cell surface doe s not depend on the cytosolic domains of the alpha- and beta-chains. I n contrast, the stability of the alpha beta-peptide complexes determin ed the efficiency of transport to the cell surface from lysosomal, but not from endosomal, compartments. In murine B lymphoma cells, SDS-uns table and -stable complexes were transported to the cell surface at al most similar rates, whereas after lysosomal relocalization or in a cel l line in which MHC class II molecules normally accumulate in lysosoma l compartments, stable complexes were preferentially addressed to the cell surface. Our results suggest that when peptide loading occurs in lysosomal compartments, selective retention and lysosomal degradation of unstable dimers result in the expression of highly stable MHC class II-peptide complexes at the APC surface.