Recognition of chlamydial antigen by HLA-B27-restricted cytotoxic T cells in HLA-B*2705 transgenic CBA (H-2k) mice.
OBJECTIVE
The association of reactive arthritis (ReA) with HLA-B27 and the presence of bacterial antigen in joints with ReA suggest that bacterial peptides might be presented by the HLA-B27 molecule and thus stimulate CD8 T cells. This study was performed to investigate the B27-restricted cytotoxic T lymphocyte (CTL) response to Chlamydia trachomatis, using the model of HLA-B27 transgenic mice.


METHODS
CBA (H-2k) mice homozygous for HLA-B*2705 and human beta2-microglobulin expression were immunized with C trachomatis or with the chlamydial 57-kd heat-shock protein (hsp57) coupled to latex beads. Cytotoxicity of lymphocytes from in vivo-primed transgenic mice was tested against C trachomatis-infected targets. Blocking experiments were performed with monoclonal antibodies (MAb) against class I major histocompatibility complex molecules.


RESULTS
A Chlamydia-specific lysis of both B27-transfected and nontransfected target cells was observed. This response could be inhibited by anti-B27 and anti-H2 MAb. CTL from mice immunized with hsp57 were not able to lyse Chlamydia-infected target cells, and Chlamydia-specific CTL could not destroy targets loaded with hsp57.


CONCLUSIONS
These results suggest the existence of at least 2 CTL populations in this mouse model: one recognizing peptide of bacteria-infected cells restricted by HLA-B*2705 and the other recognizing peptide of bacteria-infected cells restricted by the murine H-2Kk molecule. It does not appear that hsp57 is a major target for the CD8 T cell response directed against Chlamydia. This animal model opens the way for identifying bacterial epitopes presented by HLA-B27, and might thus help to clarify the pathogenesis of B27-associated diseases.
Kuon
W
W
Universitätsklinikum Benjamin Franklin, and Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Lauster
R
R
Böttcher
U
U
Koroknay
A
A
Ulbrecht
M
M
Hartmann
M
M
Grolms
M
M
Ugrinovic
S
S
Braun
J
J
Weiss
E H
EH
Sieper
J
J
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology / Q000502:physiology; D001667:Binding, Competitive; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002692:Chlamydia trachomatis / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D005260:Female; D015235:HLA-B Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000276:immunology / Q000502:physiology; D006801:Humans; D007739:L Cells / Q000502:physiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008863:Microspheres; D000091402:Prohibitins; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016827:CD8 Antigens; D000939:Epitopes; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D006360:Heat-Shock Proteins; C000717331:PHB2 protein, human; D000091402:Prohibitins; D001613:beta 2-Microglobulin