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 molecules from the endoplasmic reticulum (ER) depends on peptide binding. For MHC class II molecules, invariant chain (Ii) promotes ER exit of newly assembled, peptide-free dimers. This raises the question of whether a mechanism exists elsewhere in the cell that dictates selective expression of peptide-associated class II molecules. We report here that dissociation of MHC class II-Ii complexes at low pH and physiological temperature leads to inclusion of empty class II in protein aggregates, and that this aggregation is specifically prevented by peptide binding. Combined with data showing that antigen exposure increases cell surface class II expression on living cells by a post-translational mechanism, these results provide evidence for peptide-dependent intracellular editing of class II dimers, which limits surface expression of empty molecules unsuitable for antigen-specific T-cell activation.
Lymphocyte Biology Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892.
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Germain
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Rinker
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013696:Temperature
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain