title: New insights into the functional role of the rheumatoid arthritis shared epitope.
abstract: The shared epitope (SE) - an HLA-DRB1-encoded 5-amino acid sequence motif carried by the vast majority of rheumatoid arthritis (RA) patients - is a risk factor for severe disease. The mechanistic basis of RA-SE association is unknown. This group has previously demonstrated that the SE acts as a signal transduction ligand that activates nitric oxide and reactive oxygen species production. SE-activated signaling depends on cell surface calreticulin, a known innate immunity receptor previously implicated in immune regulation, autoimmunity and angiogenesis. Recent evidence that the SE enhances the polarization of Th17 cells, which is a key mechanism in autoimmunity, is discussed highlighting one of several potential functional effects of the SE in RA.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-5680, USA.
authors.forename: Denise E
authors.initials: DE
authors.lastname: de Almeida
authors.forename: Song
authors.initials: S
authors.lastname: Ling
authors.forename: Joseph
authors.initials: J
authors.lastname: Holoshitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D018448:Models, Immunological; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000939:Epitopes