MOLECULAR ANALYSIS OF T PALLIDUM MEMBRANE IMMUNOGENS

苍白球膜免疫原的分子分析

• 批准号: 2060396
• 负责人: MICHAEL V. NORGARD
• 金额: $ 37万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2060396
• 关键词: B lymphocyte; Escherichia coli; T lymphocyte; Treponema pallidum; antibody formation; bacterial antigens; bacterial genetics; cell adhesion; cell migration; cell population study; cellular immunity; chemical structure function; gene expression; genetic manipulation; human subject; immunological substance; laboratory rabbit; leukocyte activation /transformation; liposomes; microorganism immunology; molecular cloning; monoclonal antibody; nonblood lipoprotein; polymerase chain reaction; syphilis; syphilis test; vascular endothelium

Recently it was discovered that several of the major integral membrane immunogens of Treponema pallidum are lipoproteins. Further analyses indicate that the 47-kDa antigen, the most immunogenic and abundant among the membrane lipoproteins, possesses an as yet unclarified novel structure. In addition to the profound immunogenicities of the lipoproteins, preliminary studies suggest that they also are stimulatory for human T cells and B cells, and perhaps endothelial cells. The working hypothesis for this study is that the lipoprotein structure of these immunogens, particularly the 47-kDa novel lipoprotein structure, is responsible for some of these important biological activities. To relate structure with function, the N-terminus and site(s) of lipid attachment in the 47-kDa lipoprotein will be determined by using both genetic and biochemical strategies. Biological activities of the 47-kDa, 34-kDa, and 15-kDa lipoproteins and their relevant lipopeptides will be examined in three key areas: 1) polyclonal activation of human B cells; 2) stimulation of specific subsets of human T cells; and, 3) activation of human vascular endothelial cells. Investigations into polyclonal B cell activation may clarify many unexplained aspects of the non-treponemal (VDRL) and specific antibody responses during syphilis. Identification of responsive human T cell subpopulations will help to explain a critical area of cell-mediated immunity in syphilis that is poorly understood. A long term goal of isolating human T cells clones will help to evaluate both stimulatory as well as possibly suppressive cellular activities operative during the progression of syphilis. Endothelial cell activation to promote T cell binding and migration will be examined to understand how T. pallidum, its lipoproteins, or other constituents induce any of the characteristic inflammatory responses of syphilis. Finally, our discovery that the major immunogens of T. pallidum are lipoproteins allows us to exploit in vaccine experiments their affinity for liposome (Iscom) incorporation. Knowledge obtained in this study will clarify the roles of the lipoproteins in several of the major events in the immunopathogenesis of syphilis, and will provide a foundation for a better understanding of cell-mediated immune mechanisms operative during syphilis. The information ultimately will be useful in conceptualizing potentially novel immunologic intervention strategies for treponemal infections.

最近发现几个主要整体膜 毛颗粒的免疫原是脂蛋白。进一步分析 表明47 kDa抗原，是最免疫原性和最丰富的抗原 膜脂蛋白具有尚未清晰的新结构。 除了脂蛋白的深刻免疫原性外， 初步研究表明，它们对人类的刺激也是刺激性的 细胞和B细胞，也许是内皮细胞。工作假设 对于这项研究，这些免疫原子的脂蛋白结构， 特别是47 kDa新颖的脂蛋白结构，负责 其中一些重要的生物学活动。将结构与 功能，47 kDa中脂质附着的N末端和位点 脂蛋白将通过使用遗传和生化来确定 策略。 47-kDa，34 kDa和15 kDa的生物学活动 脂蛋白及其相关脂蛋白肽将在三个键中检查 区域：1）人类B细胞的多克隆激活； 2）刺激 人类T细胞的特定子集； 3）激活人血管 内皮细胞。对多克隆B细胞激活的研究可能 阐明非股东（VDRL）和特定的许多无法解释的方面 梅毒期间的抗体反应。识别反应敏感的人t 细胞亚群将有助于解释细胞介导的关键区域 梅毒的免疫力知之甚少。一个长期目标 隔离人T细胞克隆将有助于评估这两种刺激性 以及可能在 梅毒的进展。内皮细胞激活以促进T细胞 将检查结合和迁移，以了解T. pallidum如何 脂蛋白或其他成分诱导任何特征 梅毒的炎症反应。最后，我们发现专业 T. pallidum的免疫原是脂蛋白，使我们能够利用疫苗 实验它们对脂质体（ISCOM）掺入的亲和力。 在这项研究中获得的知识将阐明脂蛋白的作用 在梅毒的免疫发病发生的几个主要事件中， 将为更好地理解细胞介导的基础 梅毒期间的免疫机制。最终信息 将在概念化潜在的新型免疫学方面有用 挠曲性感染的干预策略。