Identification of HLA-B27-Restricted Peptides from the Chlamydia trachomatis Proteome with Possible Relevance to HLA-B27-Associated Diseases

• Published in: The Journal of immunology (1950) 2001-10, Vol.167 (8), p.4738-4746
• Main Authors: Kuon, Wolfgang, Holzhutter, Hermann-Georg, Appel, Heiner, Grolms, Martina, Kollnberger, Simon, Traeder, Alexander, Henklein, Peter, Weiss, Elisabeth, Thiel, Andreas, Lauster, Roland, Bowness, Paul, Radbruch, Andreas, Kloetzel, Peter-Michael, Sieper, Joachim
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Reactive - etiology; Arthritis, Reactive - immunology; Bacterial Proteins - immunology; CD8-Positive T-Lymphocytes - immunology; Chlamydia Infections - immunology; Chlamydia trachomatis; Chlamydia trachomatis - immunology; Cytokines - metabolism; Cytotoxicity, Immunologic; histocompatibility antigen HLA; HLA-B27 Antigen - genetics; HLA-B27 Antigen - immunology; Humans; Mice; Mice, Transgenic; Oligopeptides - immunology; Oligopeptides - metabolism; Peptide Fragments - immunology; Peptide Fragments - metabolism; Proteome - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.8.4738

The association of HLA-B27 with ankylosing spondylitis and reactive arthritis is the strongest one known between an MHC class I Ag and a disease. We have searched the proteome of the bacterium Chlamydia trachomatis for HLA-B27 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 biomathematical computer programs, the first of which predicts HLA-B27 peptide binding epitopes, and the second the probability of HLA-B27 peptide generation 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. trachomatis proteins that are stimulatory for CD8(+) T cells. Eight of these nine murine-derived peptides were recognized by cytotoxic T cells. The same strategy was used to identify B27-restricted chlamydial peptides in three patients with reactive arthritis. Eleven peptides were found to be stimulatory 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 CD8(+) T cells in patients with Chlamydia-induced arthritis. This comprehensive approach offers the possibility of clarifying the pathogenesis of B27-associated diseases.