Td. Westbay et al., DISSOCIATION OF IMMUNE DETERMINANTS OF OUTER-MEMBRANE PROTEINS OF CHLAMYDIA-PSITTACI STRAIN GUINEA-PIG INCLUSION CONJUNCTIVITIS, Infection and immunity, 62(12), 1994, pp. 5614-5623
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.