Identification of HLA-B27-restricted peptides from the Chlamydia trachomatis proteome with possible relevance to HLA-B27-associated diseases

The association of HLA-B27 with ankylosing spondylitis and reactive arthrit is is the strongest one known between an MHC class I Ag and a disease. We h ave searched the proteome of the bacterium Chlamydia trachomatis for HLA-B2 7 binding peptides that are stimulatory for CD8(+) cells both in a model of HLA-B27 transgenic mice and in patients. This was done by combining two bi omathematical computer programs, the first of which predicts HLA-B27 peptid e binding epitopes, and the second the probability of HLA-B27 peptide gener ation by the proteasome system. After preselection, immunodominant peptides were identified by Ag-specific flow cytometry. Using this approach we have identified for the first time nine peptides derived from different C. trac homatis proteins that are stimulatory for CD8(+) T cells. Eight of these ni ne murine-derived peptides were recognized by cytotoxic T cells. The same s trategy was used to identify B27-restricted chlamydial peptides in three pa tients with reactive arthritis. Eleven peptides were found to be stimulator y for patient-derived CD8(+) T cells, of which eight overlapped those found in mice. Additionally, we applied the tetramer technology, showing that a B27/chlamydial peptide containing one of the chlamydial peptides stained CD 8(+) T cells in patients with Chlamydia-induced arthritis. This comprehensi ve approach offers the possibility of clarifying the pathogenesis of B27-as sociated diseases.