IMMUNE RESPONSES TO THE MSP HOMOLOGUES IN SYPHILIS

最近在梅毒的病原体梅毒螺旋体（Treponema pallidum）中发现了一个新的12成员多态性基因家族。所编码的蛋白与树突菌主要鞘蛋白（msp）具有同源性，具有可变结构域和保守结构域的特征。我们的初步研究表明，msp同源物作为opsonic抗体的靶点，并诱导显著的免疫保护，与表面暴露一致。该项目的总体目标是确定梅毒期间对msp同源物的免疫反应的性质和功能，并检查免疫在调节msp同源物表达中的作用。本研究提出以下目标：1)确定苍白球绦虫感染过程中对单个msp变量和保守结构域的体液和细胞免疫反应，以确定msp特异性是否随着时间的推移而被识别，提示抗原变异。2)。确定针对白斑t，尼科尔斯菌株msp-同源变区和恒定区抗体的功能，在调节、中和和固定化方面。3)。测定白僵菌感染人群中msp-同源表达的多样性。4)。研究免疫反应调节苍白球中单个msp同源物表达的能力，以确定免疫在msp同源物表达中的作用。这些研究将对苍白球绦虫引起多阶段疾病并在宿主体内持续数十年的机制提供重要的见解。

A new 12-membered, polymorphic gene family has recently been identified in Treponema pallidum, the causative agent of syphilis. The encoded proteins have predicted homology to the major sheath protein (msp) of T. denticola, and are characterized by variable and conserved domains. Our preliminary studies demonstrate that the msp-homologues serve as targets of opsonic antibody and induce significant immune protection, consistent with surface exposure. The overall goal of this project is to determine the nature and function of the immune response to the msp-homologues during syphilis and to examine the role of immunity in modulating msp-homologue expression. The following aims are proposed: 1) Define the humoral and cellular immune responses to individual msp variable and conserved domains during infection with T. pallidum to determine whether msp specificities are recognized over time, suggesting antigenic variation. 2). Determine the function of antibodies directed against the msp-homologue variable and constant regions of T. pallidum, Nichols strain in terms of opsonization, neutralization and immobilization. 3.) Determine the diversity of msp- homologue expression in T. pallidum-infected population. 4.) Investigate the ability of the immune response to modulate the expression of individual msp-homologues in T. pallidum to determine the role of role of immunity in msp-homologue expression. These studies will provide significant insights into the mechanisms by which T. pallidum causes multiple stages of disease and persists in the host for decades.