DISSOCIATION OF IMMUNE DETERMINANTS OF OUTER-MEMBRANE PROTEINS OF CHLAMYDIA-PSITTACI STRAIN GUINEA-PIG INCLUSION CONJUNCTIVITIS

Chlamydia trachomatis is an important human pathogen. Research to deve lop a Chlamydia vaccine has focused on the major outer membrane protei n (MOMP). Determinants of this protein elicit serovar-specific neutral izing antibodies which are thought to play a critical role in protecti ve immunity. MOMP-specific antibody responses are highly variable in t he polymorphic population. Genetic factors which might influence the M OMP-specific immune response are consequently of particular interest. The C. psittaci strain guinea pig inclusion conjunctivitis (GPIC) is a natural pathogen of the guinea pig that causes both ocular and genita l tract infections that closely resemble those caused by C. trachomati s in humans. As such, it provides an excellent model for disease. In t his report, we explore the influence of major histocompatibility compl ex-linked genes on the MOMP-specific antibody response in mice immuniz ed with either whole GPIC elementary bodies or recombinant GPIC MOMP. Our results indicate that the MOMP-specific antibody response is major histocompatibility complex linked such that mice of the H-2(d) haplot ype are high responders while mice of the H-2(k) haplotype are low res ponders. We demonstrate that MOMP-specific B cells are present in H-2( k) strains which are, however, deficient in MOMP-specific helper T cel ls. Although immunization of low-MOMP-responder strains with whole chl amydial elementary bodies induces high levels of immunoglobulin G anti body specific for Omp2, the cysteine-rich outer membrane protein, MOMP -specific B cells are unable to receive help from Omp2-specific T cell s. The failure of intermolecular help from Omp2-specific T cells and r elated observations raise important issues regarding the processing an d presentation of chlamydial antigens and the design of optimal subuni t vaccines.