SURFACE MEMBRANE ANTIGENS OF AIDS-ASSOCIATED MYCOPLASMAS

这项提议的目标是描述结构、多样性 和新近定义的支原体表膜蛋白的表达 发酵菌，一种小型的无壁原核生物，最近被发现具有潜在的 与人类病理生物学直接相关的机会主义因素 获得性免疫缺陷综合征(艾滋病)和致命性非艾滋病 在人类和灵长类动物身上。这些抗原是突出的、完整的膜 被脂类修饰的蛋白质。他们有潜在的主要作用，如 宿主细胞相互作用的介体，免疫反应的调节物和 作为其差异表达可能允许避免 免疫识别。此外，他们是重要的潜在目标 传染病流行病学与疾病相关性的血清学分析。 最近确定了几种结构不同的表面脂蛋白 用单抗进行分析。这些蛋白质包括菌株 不同的抗原，并且在体外都经历了高频的相变。 这一特征可能反映了一个重要的分集生成系统 这些生物具有多才多艺的适应能力，可以增强它们的 有可能成为感染源和病原体。现建议(I) 目前已确定的序列和编码这些基因的其他克隆基因 抗原，(Ii)过表达重组蛋白以评估其为 血清学检测中的靶点，以及(Iii)比较结构和调节 这些基因在代表阶段的等基因克隆谱系中的特征 表达的转变，以确定分子基础。 抗原性和时相变异。将使用标准方法来识别， 克隆、测序、突变改变和表达基因； 免疫监测抗原性重组蛋白；监测基因 通过对转录本的分析，在体外表达。

The objective of this proposal is to characterize the structure, diversity and expression of recently defined surface membrane proteins of Mycoplasma fermentans, a small wall-less procaryote recently identified as a potential opportunistic agent directly associated with the pathobiology of human acquired immunodeficiency syndrome (AIDS), and with fatal non-AIDS disease in humans and primates. These antigens are prominent, integral membrane proteins modified by lipid. They have a potentially major role as mediators of host cell interactions, modulators of the immune response and as variant structures whose differential expression may allow avoidance of immune recognition. Moreover, they are important as potential targets for serological analysis of infectious epidemiology and disease association. Several of these structurally diverse surface lipoproteins recently defined by monoclonal antibodies will be analyzed. These proteins include strain variant antigens, and all undergo high-frequency phase variation in vitro. This feature may reflect an important diversity-generating system providing these organisms with versatile adaptive capability that could enhance their potential as infectious agents and pathogens. It is proposed to (i) sequence currently identified and additional cloned genes encoding these antigens, (ii) overexpress recombinant proteins for their assessment as targets in serologic assays, and (iii) compare structural and regulatory features of these genes in isogenic, clonal lineages representing phase transitions in expression, in order to determine the molecular basis for. antigenic and phase variation. Standard methods will be used to identify, clone, sequence, and mutationally alter and express genes; to immunologically monitor antigenic recombinant proteins; and to monitor gene expression in vitro by analysis of transcripts.