Chlamydia trachomatis, an obligate intracellular pathogen of humans, primarily infects the ocular and genital mucosa to cause urethritis, cervicitis, and conjunctivitis. These infections generally resolve without adverse sequelae, but in many instances infection progresses to severe inflammation leading to blindness, infertility and arthritis. These severe sequelae are major public health concerns throughout the world. An estimated 500 million people in developing countries have trachoma and an estimated 7 million are permanently blind as a result. Currently, there are about 4 million new cases of sexually transmitted chlamydial infections per year in the United States. Ascending chlamydial infections in women often lead to pelvic inflammatory disease, tubal blockage, infertility and ectopic pregnancy. An estimated 20,000 women per year in the US are thought to become involuntarily infertile as a result of chlamydial-induced pelvic inflammatory disease. Because chlamydial infections are a major public health concern a better understanding of the pathogenesis of the diseases caused by C. trachomatis is needed. The pathogenesis of chlamydial disease is thought to be immunologically mediated. Using animal models of chlamydial infection we have demonstrated that a delayed hypersensitivity response to a chlamydial 57kD protein may be involved in the pathogenesis of chlamydial disease. This chlamydial protein belongs to the family of widely conserved 6OkD stress-response proteins found in eucaryotes and procaryotes. Because of the proposed importance of the immune response to this protein and the development of the serious sequelae associated with chlamydial disease we are characterizing its antigenic properties. Sequence analysis of the genes encoding the 57kD protein from C. trachomatis and the animal pathogen C. psittaci reveals that this protein is 94% identical among chlamydial species and > 50% identical to homologous proteins from other procaryotes and eucaryotes. Preliminary data on the mapping of immunoreactive determinants of this protein reveal that the amino terminus and carboxyl terminus are immunoreactive. More complete mapping of immunoreactive antibody determinants is underway. We have been successful in purifying homogeneous preparations of the 57kD protein and can now begin studies to evaluate the T-cell responses to this protein, and the mapping of T-cell reactive epitopes. These studies will provide information useful to understanding the pathogenesis of chlamydial disease.
