title: Variations in MHC Class II Antigen Processing and Presentation in Health and Disease.
abstract: MHC class II (MHC-II) molecules are critical in the control of many immune responses. They are also involved in most autoimmune diseases and other pathologies. Here, we describe the biology of MHC-II and MHC-II variations that affect immune responses. We discuss the classic cell biology of MHC-II and various perturbations. Proteolysis is a major process in the biology of MHC-II, and we describe the various components forming and controlling this endosomal proteolytic machinery. This process ultimately determines the MHC-II-presented peptidome, including cryptic peptides, modified peptides, and other peptides that are relevant in autoimmune responses. MHC-II also variable in expression, glycosylation, and turnover. We illustrate that MHC-II is variable not only in amino acids (polymorphic) but also in its biology, with consequences for both health and disease.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110; email: unanue@wustl.edu.
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, SI-1000 Ljubljana, Slovenia; email: vito.turk@ijs.si.
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; email: j.neefjes@nki.nl.|Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Jacques
authors.initials: J
authors.lastname: Neefjes
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011110:Polymorphism, Genetic; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D000941:Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments
keywords: HLA; MHC class II; antigen presentation; autoimmunity; cathepsins; inhibitors; polymorphism; processing