The major outer membrane protein (MOMP) of C. trachomatis is a putative vaccine candidate because of its association with protective immunity. Humoral responses to MOMP epitopes have been characterized and specific protective MOMP epitopes mapped. In contrast, the role of MOMP in cell- mediated immunity (CMI) is unresolved. The initial goal of the proposal will be to characterize specifics of MOMP sequence and structure, with respect to protective CMI, during chlamydial infection. This will involve: (i) use of defined MOMP epitopes as immunogens, and (ii) analyses of T lymphocyte responses to such antigens, both in vitro and with a mouse model. Based on these studies, T-cell clones to antigens which promote increased protective antibody response and/or stimulation of protective CMI will be exploited for T-cell epitope mapping. The protective abilities of these defined MOMP epitopes will be tested in a murine genital tract infection model by 1) examining the effects of adoptive transfer of T-cell clones and 2) immunizing mice with fusion proteins containing combinations of protective predicted B and T-cell epitopes. Because studies suggest that chlamydial heat shock protein (hsp600) promotes a delayed hypersensitivity (DTH) response, hsp60 may play a role in the pathology of chlamydial infection. The second goal of the proposal, analogous to the above goal, will be to characterize specifics of hsp60 sequence and structure, in this case with respect to the immunopathology of chlamydial upper tract infection in vivo. This will involve: (i) production of a suitable quantity of recombinant hsp60 as an immunogen, and (ii) characterization of T-cell lymphocyte response both in vitro and in vivo. The role of gammadelta T lymphocytes in response to hsp60 will be examined using a newly available transgenic murine line, deficient in gammadelta T- lymphocyte populations in order to complement studies in immunologically competent animals. Finally, we propose to use the results of our studies with MOMP to begin characterizing the role of CMI in patients exposed to or infected with Chlamydia spp.
Showing the most recent 10 out of 15 publications
