RECOGNITION OF CHLAMYDIAL ANTIGEN BY HLA-B27-RESTRICTED CYTOTOXIC T-CELLS IN HLA-B-ASTERISK-2705 TRANSGENIC CBA (H-2(K)) MICE

Objective. The association of reactive arthritis (ReA) with HLA-B27 an d the presence of bacterial antigen in joints with ReA suggest that ba cterial peptides might be presented by the HLA-B27 molecule and thus s timulate CD8 T cells. This study was performed to investigate the B27- restricted cytotoxic T lymphocyte (CTL) response to Chlamydia trachoma tis, using the model of HLA-B27 transgenic mice. Methods. CBA (H-2k) m ice homozygous for HLA-B2705 and human beta(2)-microglobulin expressi on were immunized with C trachomatis or with the chlamydial 57-kd heat -shock protein (hsp57) coupled to latex beads. Cytotoxicity of lymphoc ytes from in vivo-primed transgenic mice was tested against C trachoma tis-infected targets. Blocking experiments were performed with monoclo nal 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 hs p57 were not able to lyse Chlamydia-infected target cells, and Chlamyd ia-specific CTL could not destroy targets loaded with hsp57. Conclusio n. These results suggest the existence of at least 2 CTL populations i n this mouse model: one recognizing peptide of bacteria-infected cells restricted by HLA-B2705 and the other recognizing peptide of bacteri a-infected cells restricted by the murine H-2K(k) molecule. It does no t appear that hsp57 is a major target for the CD8 T cell response dire cted against Chlamydia. This animal model opens the way for identifyin g bacterial epitopes presented by HLA-B27, and might thus help to clar ify the pathogenesis of B27-associated diseases.