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

Abstract

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.

• Authors: W Kuon, H G Holzhütter, H Appel, M Grolms, S Kollnberger, A Traeder, P Henklein, E Weiss, A Thiel, R Lauster, P Bowness, A Radbruch, P M Kloetzel, J Sieper
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 167 Issue 8 Pg. 4738-46 (Oct 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11591805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Cytokines
• HLA-B27 Antigen
• Oligopeptides
• Peptide Fragments
• Proteome

Topics

• Animals
• Arthritis, Reactive (etiology, immunology)
• Bacterial Proteins (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Chlamydia Infections (immunology)
• Chlamydia trachomatis (immunology)
• Cytokines (metabolism)
• Cytotoxicity, Immunologic
• HLA-B27 Antigen (genetics, immunology)
• Humans
• Mice
• Mice, Transgenic
• Oligopeptides (immunology, metabolism)
• Peptide Fragments (immunology, metabolism)
• Proteome (immunology)