Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain.
HLA class II molecules are heterodimeric transmembrane glycoproteins that bind and present processed antigenic peptides to CD4-positive T lymphocytes. Intracellularly, class II molecules associate with a third subunit termed the invariant (I) chain. Here we describe the physical characteristics of the intracellular class II alpha beta I complex. Chemical crosslinking, size exclusion chromatography and sedimentation velocity studies demonstrate that the alpha beta I complex is a nine-subunit transmembrane protein that contains three alpha beta dimers associated with an I chain trimer. The organization of class II alpha- and beta-subunits in such a multimer may have a role in the documented ability of the I chain to inhibit peptide binding to class II molecules. In addition, the formation of the nine-chain complex may induce the structural changes necessary to overcome the cytoplasmic retention signal responsible for the localization of free I chain in the endoplasmic reticulum, releasing class II-I chain complexes for transport to endosomes.
Roche
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Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
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Cresswell
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D000944:Antigens, Differentiation, B-Lymphocyte; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006681:HLA-D Antigens / Q000737:chemistry* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D015394:Molecular Structure; D008985:Monensin / Q000494:pharmacology; D011485:Protein Binding
D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; C045084:invariant chain; D008985:Monensin