Bacteria-specific Cytotoxic CD8+T Cells: A Missing Link in the Pathogenesis of the HLA-B27-associated Spondylarthropathies

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Abstract
The term seronegative spondylarthropathies is used for an entity of rheumatic syndromes of peripheral joints and the spine (ankylosing spondylitis, reactive arthritis, Reiter's syndrome, arthritis in psoriasis and in inflammatory bowel disease) which are strongly associated with the MHC class I molecule HLA-B27. However, the mechanisms whereby HLA-B27 confers disease susceptibility have so far remained unknown. There is strong evidence that gut inflammation and infection with gram-negative bacteria play a role in the induction of B27-associated disease. HLA-B27, like other MHC class I molecules, physiologically binds antigenic peptides in its binding groove and presents them to CD8+ T lymphocytes. Consequently, if the disease association with HLA-B27 arises from its role as a T-cell restriction element, synovial fluid CD8+ rather than CD4+ T cells should play a prominent pathogenetic role and should be detectable within the affected joints. In this paper, recent studies on bacteria-specific cytotoxic T cells and on peptide binding to HLA-B27 are reviewed. Particular emphasis is laid on the role of HLA-B27 restricted synovial CD8+ T cells with specificity for bacterial antigens or autoantigens. These cytotoxic T cells could provide a missing link in the pathogenesis of the spondylarthropathies and could now serve as tools to identify the critical antigenic epitopes of bacterial and self peptides which are involved in disease induction.