title: Mediation by HLA-DM of dissociation of peptides from HLA-DR.
abstract: Human leukocyte antigen (HLA)-DM is an unconventional major histocompatibility complex (MHC) class II heterodimer that is important for B-cell-mediated antigen processing and presentation to MHC class II-restricted T cells. HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region, and shares some homology with MHC class I and class II proteins. Here we define the biochemical role of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purified from culture supernatants of insect cell transformants. At pH 5.0, they induce the dissociation of a subset of peptides bound to HLA-DR, including a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced binding of exogenous peptides.
authors.affiliation: Department of Autoimmune Disease Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: V S
authors.initials: VS
authors.lastname: Sloan
authors.forename: P
authors.initials: P
authors.lastname: Cameron
authors.forename: G
authors.initials: G
authors.lastname: Porter
authors.forename: M
authors.initials: M
authors.lastname: Gammon
authors.forename: M
authors.initials: M
authors.lastname: Amaya
authors.forename: E
authors.initials: E
authors.lastname: Mellins
authors.forename: D M
authors.initials: DM
authors.lastname: Zaller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004330:Drosophila; D006681:HLA-D Antigens / Q000502:physiology*; D006684:HLA-DR Antigens / Q000737:chemistry / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D011487:Protein Conformation; D014170:Transformation, Genetic
chemical_list: 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; D009842:Oligopeptides; C045084:invariant chain