HUMAN IGG SUBCLASS-SPECIFIC BACTERIAL BINDING PROTEINS

拟议研究的重点是制定一个详细的分类 对于A组链球菌表达的II型免疫球蛋白结合蛋白和 了解这些分子在链球菌感染或 感染后的后遗症。最初的重点将是开发 血清学和基因探针分析定性和定量 不同形式的免疫球蛋白结合蛋白(S)的表达 A组菌株。一旦一个详细的分类系统被 一旦确定，这些技术将被应用于描述II型 A群新鲜临床分离株免疫球蛋白结合蛋白的表达 链球菌，以确定是否有关联 免疫球蛋白结合的定性或定量表达之间的差异 蛋白质与儿童感染后后遗症的病程 从其身上恢复病毒的患者。 免疫球蛋白结合蛋白的生物活性将用 各种体外和体内检测系统。这些研究将 涉及具有明确的免疫球蛋白结合蛋白表达的A组菌株 以及检测插入II型免疫球蛋白结合蛋白的效果 将该基因(S)克隆到一株免疫球蛋白结合蛋白阴性的戈登氏链球菌中。 体外系统将测量细菌表达类型的能力 II免疫球蛋白结合蛋白在人体血液中存活的同时体内 系统将把重点放在细菌建立致命病毒的能力上 当注射到小鼠的皮肤中时会受到感染。这些研究将是 旨在证明表达II型免疫球蛋白结合的重要性 蛋白质。M蛋白免疫球蛋白结合蛋白杂交体的潜在作用 分子在免疫复合体的形成中可能有助于 链球菌病后肾小球肾炎也将被检查。已被占用 总之，这些对II型免疫球蛋白结合蛋白的研究应该会产生新的 关于这些分子的多样性及其潜在作用的信息 在建立侵袭性链球菌感染以及他们的 可能对感染后的后遗症有贡献。

The focus of the proposed studies is to develop a detailed classification for type II IgG-binding proteins expressed by group A streptococci and to understand the role of these molecules in streptococcal infection or post-infection sequelae. The initial focus will be to develop serological and gene probes to analyze the qualitative and quantitative expression of different forms of IgG-binding protein(s) expressed by group A strains. Once a detailed classification system has been established, these techniques will be applied to characterize the type II IgG-binding proteins expressed on fresh clinical isolates of group A streptococci in order to determine whether there is an association between the qualitative or quantitative expression of IgG-binding proteins and the course of infection of post-infection sequelae in the patient from which the strain was recovered. The biological activities of IgG-binding proteins will be explored using a variety of in vitro and in vivo assay systems. These studies will involve group A strains with defined IgG-binding protein expression as well as examining the effect of insertion of type II IgG-binding protein gene(s) into an IgG-binding protein negative S. gordonii Challis strain. The in vitro system will measure the ability of bacteria expressing type II IgG-binding proteins to survive in human blood while the in vivo system will focus on the ability of the bacteria to establish lethal infections when injected into the skin of mice. These studies will be designed to document the importance of expression of type II IgG-binding proteins. The potential role for an M protein IgG-binding protein hybrid molecule in the formation of immune complexes that could contribute to post-streptococcal glomerulo-nephritis will also be examined. Taken together, these studies of type II IgG-binding proteins should yield new information on the diversity of these molecules and their potential role in establishing invasive streptococcal infections as well as their possible contributions to post-infection sequelae.