title: HLA , CTLA-4 and PTPN22 : the shared genetic master-key to autoimmunity?
abstract: Several genetic loci appear to be involved in susceptibility to autoimmune disease. Some loci are disease specific, whereas others appear to exert a general effect on the autoimmune disease process. Despite a large number of studies of many different diseases, consistent associations with multiple autoimmune disorders have been restricted to three gene regions: the human leukocyte antigen (HLA) class II region on chromosome 6p21, the gene encoding cytotoxic T lymphocyte-associated 4 (CTLA-4) on chromosome 2q33, and the PTPN22 gene encoding lymphoid tyrosine phosphatase (LYP) on chromosome 1p13. Each of these loci is likely to encode molecules that are crucial in the immune cascade and are actively involved in T-cell activation. Moreover, gene polymorphisms that affect function might contribute to the triggering of autoimmune disease by as-yet-unknown mechanisms. This review summarises recent developments and current understanding of the way in which molecules encoded by these susceptibility loci contribute to T-cell activation, and hypothesises how aberrant function of these molecules might trigger autoimmunity.
authors.affiliation: Department of Medicine, Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Wolfson Drive, Edgbaston, Birmingham, B15 2TT, UK. ojb049@bham.ac.uk
authors.forename: Oliver
authors.initials: O
authors.lastname: Brand
authors.forename: Stephen
authors.initials: S
authors.lastname: Gough
authors.forename: Joanne
authors.initials: J
authors.lastname: Heward
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D000943:Antigens, Differentiation / Q000235:genetics* / Q000502:physiology; D001327:Autoimmune Diseases / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics* / Q000502:physiology; D006801:Humans; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000502:physiology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006680:HLA Antigens; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases