Westbay T D, Dascher C C, Hsia R C, Bavoil P M, Zauderer M
Department of Microbiology, University of Rochester Medical Center, New York 14642.
Infect Immun. 1994 Dec;62(12):5614-23. doi: 10.1128/iai.62.12.5614-5623.1994.
Chlamydia trachomatis is an important human pathogen. Research to develop a Chlamydia vaccine has focused on the major outer membrane protein (MOMP). Determinants of this protein elicit serovar-specific neutralizing antibodies which are thought to play a critical role in protective immunity. MOMP-specific antibody responses are highly variable in the polymorphic population. Genetic factors which might influence the MOMP-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 genital tract infections that closely resemble those caused by C. trachomatis in humans. As such, it provides an excellent model for disease. In this report, we explore the influence of major histocompatibility complex-linked genes on the MOMP-specific antibody response in mice immunized 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-2d haplotype are high responders while mice of the H-2k haplotype are low responders. We demonstrate that MOMP-specific B cells are present in H-2k strains which are, however, deficient in MOMP-specific helper T cells. Although immunization of low-MOMP-responder strains with whole chlamydial elementary bodies induces high levels of immunoglobulin G antibody specific for Omp2, the cysteine-rich outer membrane protein, MOMP-specific B cells are unable to receive help from Omp2-specific T cells. The failure of intermolecular help from Omp2-specific T cells and related observations raise important issues regarding the processing and presentation of chlamydial antigens and the design of optimal subunit vaccines.
沙眼衣原体是一种重要的人类病原体。开发衣原体疫苗的研究主要集中在主要外膜蛋白（MOMP）上。该蛋白的决定簇可引发血清型特异性中和抗体，这些抗体被认为在保护性免疫中起关键作用。在多态性群体中，MOMP特异性抗体反应高度可变。因此，可能影响MOMP特异性免疫反应的遗传因素备受关注。鹦鹉热衣原体豚鼠包涵体结膜炎（GPIC）菌株是豚鼠的一种天然病原体，可引起眼部和生殖道感染，与人类沙眼衣原体引起的感染极为相似。因此，它为疾病提供了一个极好的模型。在本报告中，我们探讨了主要组织相容性复合体相关基因对用全GPIC原体或重组GPIC MOMP免疫的小鼠中MOMP特异性抗体反应的影响。我们的结果表明，MOMP特异性抗体反应与主要组织相容性复合体相关，使得H-2d单倍型的小鼠是高反应者，而H-2k单倍型的小鼠是低反应者。我们证明，MOMP特异性B细胞存在于H-2k菌株中，然而，这些菌株缺乏MOMP特异性辅助性T细胞。尽管用全衣原体原体免疫低MOMP反应株会诱导高水平的针对富含半胱氨酸的外膜蛋白Omp2的免疫球蛋白G抗体，但MOMP特异性B细胞无法从Omp2特异性T细胞获得帮助。Omp2特异性T细胞的分子间帮助失败及相关观察结果提出了关于衣原体抗原的加工和呈递以及最佳亚单位疫苗设计的重要问题。
