title: Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules. Proc. Natl. Acad. Sci. USA. 1991. 88: 3150-3154.
abstract: HLA-DR molecules are heterodimeric transmembrane glycoproteins that associate intracellularly with a polypeptide known as the invariant (I) chain. Shortly before expression of the HLA-DR αβ dimer on the cell surface, however the I chain is removed from the intracellular αβI complex by a mechanism thought to involve proteolysis . In this report, we show that treatment of purified αβI with the cysteine proteinase cathepsin B results in the specific proteolysis of the HLA-DR-associated I chain in vitro. As a consequence of this, the I chain is removed and free αβ dimers are released from αβI. Although αβI fails to bind an immunogenic peptide, the released αβ dimers acquire the ability to bind the peptide after proteolysis of the I chain. These results suggest that the I chain inhibits immunogenic peptide binding to αβI early during intracellular transport and demonstrate that proteolysis is likely to be the in vivo mechanism of I chain removal.
authors.affiliation: Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Roche
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000266:history*; D002461:Cell Line, Transformed; D004705:Endocytosis / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000266:history*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000266:history*; D049673:History, 20th Century; D006801:Humans; D006868:Hydrolysis; D007424:Intracellular Fluid / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000266:history*; D011485:Protein Binding / Q000276:immunology; D055503:Protein Multimerization / Q000276:immunology; D021381:Protein Transport / Q000276:immunology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C045084:invariant chain