SURFACE MEMBRANE ANTIGENS OF AIDS-ASSOCIATED MYCOPLASMAS

该提案的目的是描述结构、多样性 和表达最近定义的支原体表面膜蛋白 fermentans，一种小型无壁原核生物，最近被确定为一种潜在的 与人类疾病病理学直接相关的机会性病原体 获得性免疫缺陷综合症（艾滋病），以及致命的非艾滋病疾病 在人类和灵长类动物中。 这些抗原是突出的，完整的膜 被脂质修饰的蛋白质。 他们有一个潜在的主要作用， 宿主细胞相互作用的介质，免疫应答的调节剂， 作为变体结构，其差异表达可以避免 免疫识别 此外，它们是重要的潜在目标， 传染病流行病学和疾病关联的血清学分析。 这些结构多样的表面脂蛋白中有几种最近被定义为 单克隆抗体将被分析。 这些蛋白质包括 变体抗原，并且都在体外经历高频相位变化。 这一特点可能反映了一个重要的多样性生成系统， 这些生物具有多种适应能力，可以提高它们的 潜在的传染源和病原体。 建议：（一） 目前鉴定的序列和编码这些序列的另外的克隆基因 抗原，（ii）过表达重组蛋白，用于它们作为 血清学测定中的靶点，以及（iii）比较结构和调节 这些基因在同基因克隆谱系中的特征代表了阶段 表达的转变，以确定的分子基础。 抗原性和相位变化。 标准方法将用于识别， 克隆，测序，突变改变和表达基因; 免疫学监测抗原性重组蛋白;以及监测基因 通过分析转录物体外表达。

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.