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 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.
Kuon
W
W
Medical Department I, Klinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.
Holzhütter
H G
HG
Appel
H
H
Grolms
M
M
Kollnberger
S
S
Traeder
A
A
Henklein
P
P
Weiss
E
E
Thiel
A
A
Lauster
R
R
Bowness
P
P
Radbruch
A
A
Kloetzel
P M
PM
Sieper
J
J
D000818:Animals; D016918:Arthritis, Reactive / Q000209:etiology / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology; D002692:Chlamydia trachomatis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D020543:Proteome / Q000276:immunology*
D001426:Bacterial Proteins; D016207:Cytokines; D015796:HLA-B27 Antigen; D009842:Oligopeptides; D010446:Peptide Fragments; D020543:Proteome