title: Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases.
abstract: Misfolded proteins localized in the endoplasmic reticulum are degraded promptly and thus are not transported outside cells. However, misfolded proteins in the endoplasmic reticulum are rescued from protein degradation upon association with major histocompatibility complex (MHC) class II molecules and are transported to the cell surface by MHC class II molecules without being processed to peptides. Studies on the misfolded proteins rescued by MHC class II molecules have revealed that misfolded proteins associated with MHC class II molecules are specific targets for autoantibodies produced in autoimmune diseases. Furthermore, a strong correlation has been observed between autoantibody binding to misfolded proteins associated with MHC class II molecules and the autoimmune disease susceptibility conferred by each MHC class II allele. These new insights into MHC class II molecules suggest that misfolded proteins rescued from protein degradation by MHC class II molecules are recognized as "neo-self" antigens by immune system and are involved in autoimmune diseases as autoantibody targets.
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan. Electronic address: arase@biken.osaka-u.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D058990:Molecular Targeted Therapy; D017510:Protein Folding; D021381:Protein Transport / Q000276:immunology; D059748:Proteolysis; D012217:Rheumatoid Factor / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D012217:Rheumatoid Factor
keywords: APS; Antigen presentation; Antiphospholipid syndrome; Autoantibody; HLA; Misfolded protein; RA; Rheumatoid arthritis; cryptic epitope; human leukocyte antigen; molecular chaperon