DIVERSITY OF CTL EPITOPES AND CHLAMYDIA

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Chlamydia is the most prevalent cause of bacterial sexually transmitted disease in the developed world, Causing both overt disease and infertility, and is also the leading cause of preventable blindness worldwide. Natural immunity against Chlamydia and the vaccine strategies that have been attempted to date provide protection against only limited serovars. The goal of these studies is to ascertain whether a vaccine strategy which primes a cytotoxic T-lymphocyte (CTL) response can provide protection against a wide range of Chlamydia serovars. We have cultured Chlamydia reactive CTL from infected mice and have shown that they are specific for and lyse Chlamydia infected cells in vitro. Upon adoptive transfer of these CTL into Chlamydia infected mice, a reduction in bacterial load can be measured in the spleen. The initial experiments in this proposal will determine whether CTL specific for Chlamydia can be primed in mice of different MHC haplotypes. Other experiments characterize the diversity of antigens recognized by Chlamydia specific CTL and whether the diversity of antigens recognized by CTL primed by genital infection differ from those primed intraperitoneally. Thirdly, we propose to determine which of these antigens can prime CTL which are both protective and cross-reactive between Chlamydia serovars. This project will contribute to the overall program by characterizing at the cellular and molecular level antigens which are important in a protective CTL response. The project will complement project 3 which proposes in part to examine the CTL response elicited by Chlamydia infection in humans. This project is dependent on the resources provided by the laboratory (D) and statistical (B) cores. By providing novel information about the protective CTL response engendered during Chlamydia STD, this project will contribute to the overall objective of developing a vaccine to prevent and control these infections.