Originally published In Press as doi:10.1074/mcp.M900107-MCP200 on May 13, 2009.
Molecular & Cellular Proteomics 8:1850-1859, 2009.
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
Research
Endogenous Processing and Presentation of T-cell Epitopes from Chlamydia trachomatis with Relevance in HLA-B27-associated Reactive Arthritis*,
Juan J. Cragnolini,
Noel García-Medel and
José A. López de Castro
From the Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Universidad Autónoma, 28049 Madrid, Spain
Chlamydia trachomatis triggers reactive arthritis, a spondyloarthropathy linked to the human major histocompatibility complex molecule HLA-B27, through an unknown mechanism that might involve molecular mimicry between chlamydial and self-derived HLA-B27 ligands. Chlamydia-specific CD8+ T-cells are found in reactive arthritis patients, but the immunogenic epitopes are unknown. A previous screening of the chlamydial genome for putative HLA-B27 ligands predicted multiple peptides that were recognized in vitro by CD8+ T-lymphocytes from patients. Here stable transfectants expressing bacterial fusion proteins in human cells were generated to investigate the endogenous processing and presentation by HLA-B27 of two such epitopes through comparative immunoproteomics of HLA-B27-bound peptide repertoires. A predicted T-cell epitope, from the CT610 gene product, was presented by HLA-B27. This is, to our knowledge, the first endogenously processed epitope involved in HLA-B27-restricted responses against C. trachomatis in reactive arthritis. A second predicted epitope, from the CT634 gene product, was not detected. Instead a non-predicted nonamer from the same protein was identified. Both bacterial peptides showed very high homology with human sequences containing the HLA-B27 binding motif. Thus, expression and intracellular processing of chlamydial proteins into human cells allowed us to identify two bacterial HLA-B27 ligands, including the first endogenous T-cell epitope from C. trachomatis involved in spondyloarthropathy. That human proteins contain sequences mimicking chlamydial T-cell epitopes suggests a basis for an autoimmune component of Chlamydia-induced HLA-B27-associated disease.
To whom correspondence should be addressed: Centro de Biología Molecular Severo Ochoa, c/ Nicolás Cabrera N. 1, Universidad Autónoma, 28049 Madrid, Spain. Tel.: 34-91-196-4554; Fax: 34-91-196-4420; E-mail: aldecastro{at}cbm.uam.es.

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Copyright © 2009 by the American Society for Biochemistry and Molecular Biology.
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