THE PATHOGENESIS OF HLA-B27 ASSOCIATED ARTHRITIS - LESSONS FROM THE B27 CRYSTAL

The most remarkable association between a major histocompatibility com plex antigen and disease susceptibility - HLA-B27 and seronegative spo ndyloarthropathies, particularly ankylosing spondylitis - was discover ed 20 years ago. During the two intervening decades advances in basic immunology and molecular biology have not only revealed the biosynthes is and structure of HLA-B27 but also given clues to the basic function of this molecule, the presentation of allele-specific peptides to CD8 + cytotoxic T cells. The recently reported three-dimensional structure of HLA-B27 and the identification of self-peptides bound to this majo r histocompatibility complex class I antigen can be viewed as a landma rk in the understanding of the pathogenic role of HLA-B27. Based on cr ystallographic evidence, a peptide-binding motif can be postulated tha t should allow identification of HLA-B27 complexed peptides which may trigger an immune reaction causing arthritis.