PEPTIDE BINDING INHIBITS PROTEIN AGGREGATION OF INVARIANT-CHAIN FREE CLASS-II DIMERS AND PROMOTES SURFACE EXPRESSION OF OCCUPIED MOLECULES

EFFICIENT egress of major histocompatibility complex (MHC) class I mol ecules from the endoplasmic reticulum (ER) depends on peptide binding1 -7. For MHC class II molecules, invariant chain (Ii) promotes ER exit of newly assembled, peptide-free dimers8-14. This raises the question of whether a mechanism exists elsewhere in the cell that dictates sele ctive expression of peptide-associated class II molecules. We report h ere that dissociation of MHC class II-Ii complexes at low pH and physi ological temperature leads to inclusion of empty class II in protein a ggregates, and that this aggregation is specifically prevented by pept ide binding. Combined with data showing that antigen exposure increase s cell surface class II expression on living cells by a post-translati onal mechanism12, these results provide evidence for peptide-dependent intracellular editing of class II dimers, which limits surface expres sion of empty molecules unsuitable for antigen-specific T-cell activat ion.