Intracellular formation and cell surface expression of a complex of an intact lysosomal protein and MHC class II molecules.
The generation of invariant chain-free MHC class II molecules and their association with endocytically generated peptides are thought to occur in specialized lysosome-like compartments called MIICs (MHC class II compartments). A number of in vitro studies have shown that large denatured proteins can bind to class II molecules, and that class II association can protect the bound segment of protein from proteolytic degradation. In this work, we present what we believe is the first example of an intact endogenous protein (IP30) binding in an allele-dependent fashion to class II molecules in vivo. IP30 is an IFN-gamma-inducible 35-kDa glycoprotein that localizes in MIICs. In this study, we show that intact IP30 binds to certain HLA-DR alleles via an N-terminal prosequence. The association takes place in the endocytic pathway following removal of invariant chain from class II molecules and before their cell surface expression. We also show that DR-IP30 complexes are SDS stable. The potential precursor-product relationship between DR-IP30 complexes and the DR-peptide complex is discussed.
Arunachalam
B
B
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA.
Pan
M
M
Cresswell
P
P
D000483:Alleles; D000818:Animals; D002472:Cell Transformation, Viral; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006681:HLA-D Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D008247:Lysosomes / Q000276:immunology; D051379:Mice; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011506:Proteins / Q000276:immunology*; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate; D013499:Surface Properties
C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011506:Proteins; D012967:Sodium Dodecyl Sulfate; D010088:Oxidoreductases; C483811:Ifi30 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors