title: Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases.
abstract: The major function of major histocompatibility complex (MHC) class II molecules is the presentation of peptide antigens to helper T cells. However, when misfolded proteins are associated with MHC class II molecules in the endoplasmic reticulum, they are transported to the cell surface by MHC class II molecules without processing to peptides. Of note, misfolded proteins complexed with MHC class II molecules are specifically recognized by 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 associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins rescued from degradation by MHC class II molecules may be recognized as 'neo-self' antigens by the immune system and be involved in the pathogenicity of autoimmune diseases.
authors.affiliation: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; and.
authors.forename: Noriko
authors.initials: N
authors.lastname: Arase
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 arase@biken.osaka-u.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000378:metabolism*; D001323:Autoantibodies / Q000032:analysis / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D008954:Models, Biological; D011110:Polymorphism, Genetic; D021381:Protein Transport; D059748:Proteolysis; D057165:Proteostasis Deficiencies / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies
keywords: antigen presentation; cryptic epitope; human leukocyte antigen (HLA); molecular chaperon; rheumatoid arthritis