title: Intracellular and cell surface heterotypic associations of human leukocyte antigen-DR and human invariant chain.
abstract: The intracellular and cell-surface heterotypic associations of HLA-DR in the presence and absence of the invariant chain were investigated. Simultaneous confocal microscopy imaging of the Golgi apparatus and HLA-DR molecules revealed that cells transfected only with HLA-DR and not the invariant chain or HLA-DM, accumulate class II molecules mostly in the Golgi apparatus, proximal to the cell nucleus. In contrast, in cells transfected with both HLA-DR and the invariant chain, or HLA-DR, the invariant chain and HLA-DM, the class II molecules are more evenly distributed in intracellular compartments. Confocal microscopy and flow cytometry revealed that in the absence of the invariant chain, a greater number of HLA-DR molecules are transported to the cell surface. Biochemical experiments and nonequilibrium pH gradient electrophoresis revealed that HLA-DR associates with surface invariant chain in the presence of HLA-DM. In cells that lack HLA-DM, no cell-surface association of HLA-DR and Ii was observed. Taken together, these results reveal two separate and distinct functions for surface and intracellular invariant chain subsets. The intracellular invariant chain "arrests" the class II molecules in the endocytic pathway. In contrast, cell-surface invariant chain associates with class II molecules at the cell surface, possibly playing a role in recycling empty class II molecules or as an accessory molecule.
authors.affiliation: University of Essex, Department of Biological Sciences, Colchester, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Triantafilou
authors.forename: M
authors.initials: M
authors.lastname: Triantafilou
authors.forename: K M
authors.initials: KM
authors.lastname: Wilson
authors.forename: R J
authors.initials: RJ
authors.lastname: Cherry
authors.forename: N
authors.initials: N
authors.lastname: Fernandez
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D006056:Golgi Apparatus / Q000276:immunology; D006681:HLA-D Antigens / Q000737:chemistry / Q000378:metabolism; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D014162:Transfection
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; D046911:Macromolecular Substances; C045084:invariant chain