DR 4 - IE transgenic mice
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چکیده
JEM © The Rockefeller University Press $30.00 Vol. 205, No. 4, April 14, 2008 967-979 www.jem.org/cgi/doi/ 967 10.1084/jem.20072051 Rheumatoid arthritis (RA) is a chronic disease aff ecting the peripheral joints in which abnormalities in the synovium precipitate a destructive process that often leads to cartilage and bone erosion. The autoimmune nature of this disease has been defi ned, in part, through the presence of IgG autoantibodies such as rheumatoid factor and a tight genetic association with MHC class II molecules that contain a motif known as the shared epitope (SE) ( 1, 2 ). This SE forms one of the major MHC class II anchoring pockets (known as P4) and imparts the ability to preferentially interact with certain amino acid side chains from antigenic peptides for subsequent presentation to CD4 T cells ( 3 ). Because of these properties, the adaptive arm of the immune system has been implicated in driving disease pathogenesis through autoantigen recognition. Although many candidate autoantigens have been investigated in RA, a frequent target of the immune response found predominantly in this patient population has been lacking until recently. The discovery of serum IgG autoantibodies from RA patients that bind posttranslationally modifi ed arginine (citrulline) within the context of certain proteins/peptides has provided an excellent diagnostic tool due in large part to their disease specifi city ( 4 – 7 ). The propensity to develop anti-citrulline antibodies is also associated with the expression of the SE, suggesting that an MHC class II – restricted CORRESPONDENCE Ewa Cairns: [email protected]
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