title: Misfolded proteins complexed with MHC class II molecules are targets for autoantibodies.
abstract: Major histocompatibility complex (MHC) molecule is important for immune system through its function of presentation of peptide antigens. MHC is the gene most strongly associated with susceptibility to many autoimmune diseases. We recently found a novel function of MHC class II molecules to transport cellular misfolded proteins to the cell surface without processing to peptides. Interestingly, misfolded proteins transported to the cell surface by MHC class II molecules were found to be a specific targets for autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is strongly associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins associated with MHC class II molecules might be involved in the pathogenesis of autoimmune diseases.
authors.affiliation: Laboratory of Immunochemistry, World Premier International (WPI) Immunology Frontier Research Center.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hiwa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D000483:Alleles; D017951:Antigen Presentation; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D046912:Multiprotein Complexes; D011485:Protein Binding; D017510:Protein Folding; D021381:Protein Transport
chemical_list: D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; D046912:Multiprotein Complexes