Genetics of Rheumatoid Arthritis

  • Gerald T Nepom1

    Affiliated with

    Arthritis Res19991(Suppl 1):S01

    DOI: 10.1186/ar15

    Published: 15 November 1999

    Full text

    Genetic associations between rheumatoid arthritis and specific HLA class II genes provide clues to understanding the molecular basis for disease susceptibility. There is a remarkable structural relationship among different rheumatoid arthritis (RA) susceptibility genes, in which each of the associated class II alleles encodes a sequence of key amino acids termed the `shared epitope.' Mechanistic models to account for the shared epitope association with RA can be interpreted in the context of an HLA-directed pathway for the development of disease. We suggest that altered T cell activation results from recognition of the shared epitope, providing a potential mechanism by which the shared epitope may be involved in the generation or modulation of self-recognition during antigen presentation and processing. We propose that the shared epitope association with RA is not solely based on a specific peptide binding motif and peptide determinant selection but rather is influenced by a strongly biased direct recognition of shared epitope residues by direct T cell contact.

    Authors’ Affiliations

    Virginia Mason Research Center


    1. Nepom GT: Major histocompatibility complex-directed susceptibility to rheumatoid arthritis. Adv Immunol 1998, 68:315–332.View ArticlePubMed


    © Current Science Ltd 2000