DM enhances peptide binding to class II MHC by release of invariant chain-derived peptide.
Major histocompatibility complex (MHC) class II molecules bind antigenic peptides rapidly after biosynthesis in antigen-presenting cells (APCs). By contrast, the rate of peptide binding to purified class II molecules is remarkably slow. We find that purified HLA-DR molecules bind peptides rapidly in the presence but not the absence of HLA-DM, a recently identified heterodimer required for efficient antigen processing. The same effect is seen with immunoprecipitated DM, suggesting that DM interacts directly with DR. Class II-associated invariant chain peptides (CLIP) are selectively and rapidly released from DR during incubation with DM at pH 5. We conclude that DM is a cofactor that enhances peptide binding to DR molecules through a mechanism involving peptide exchange.
Sherman
M A
MA
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Weber
D A
DA
Jensen
P E
PE
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001483:Base Sequence; D006681:HLA-D Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding
D000944:Antigens, Differentiation, B-Lymphocyte; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D010455:Peptides; C045084:invariant chain