Recognition of chlamydial antigen by HLA-B27-restricted cytotoxic T cells in HLA-B super()2705 transgenic CBA (H-2 super(k)) mice

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. CBA (H-2 super(k)) mice homozygous for HLAB super(*)2705 and human beta sub(2)-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. 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. 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 super(*)2705 and the other recognizing peptide of bacteria-infected cells restricted by the murine H-2K super(k) 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.