AUTO-ANTI-CD4 ANTIBODIES IN HIV INFECTION

人CD 4作为人类免疫缺陷病毒受体的作用 (HIV)已经导致了对CD 4-gp 12 O的分子性质的广泛研究 交互. 数据支持抗淋巴细胞抗体 抗体可能在HIV疾病过程中起关键作用， 保护性或致病性。 来自HIV感染者的血清将被 筛查抗CD 4抗体，这些抗体将被 其特征在于CD 4结合，阻断许多重组 gp 120，以及通过不同的病毒分离株中和感染。 的 自身抗CD 4在HIV疾病进展中的潜在作用将是 通过测定抗血清的免疫细胞病变效应来评估。 在 此外，还将跟踪选定患者的免疫表型特征 特别注意结合到抗体的自身抗体的存在。 细胞的表面。 蛋白质结构的持续分析涉及 抗体和包膜糖蛋白结合表位的表达 使用选择的CD 4突变体提出了CD 4。 使用这些试剂， 抗CD 4自身抗体间相互作用的分子本质 在感染艾滋病病毒期间，将进行调查。 可能的 自体抗CD 4抗体之间存在分子模拟， 还将评价病毒gp 120。 从选定的个体中，抗CD 4 产生抗体的淋巴细胞将用于产生组合的 免疫球蛋白表达文库以克隆和表达抗CD 4 抗体的 然后将这些重组Fab进行表征 在结构上，并针对与天然和突变的CD 4的结合进行定位。 他们 将分析它们阻断不同重组体的能力， gp 120，并在体外抑制病毒感染。 结构信息 与病毒/CD 4相互作用有关， 免疫干预和/或合理的药物设计将通过 这些进一步的分子表征。

The role of human CD4 as the receptor for human immunodeficiency virus (HIV) has led to extensive study of the molecular nature of CD4-gpl2O interactions. Data supports the hypothesis that anti-lymphocyte antibodies may play a critical role in the course of HIV disease, either protective or pathogenic. Sera from HIV infected individuals will be screened for anti-CD4 antibodies and those antibodies will be characterized for CD4 binding, blocking of a number of recombinant gpl2O's, and neutralization of infection by distinct viral isolates. The potential role of auto-anti-CD4 in the progression of HIV disease will be assessed by assaying the antisera for immunocytopathic effects. In addition, immunophenotypic profiles of select patients will be followed with particular attention to the presence of auto-antibodies bound to the surface of cells. Continued analyses of protein structure involved in expression of the antibody and envelope glycoprotein binding epitopes on CD4 are proposed using select CD4 mutants. Using these reagents, the molecular nature of interactions between auto-antibodies against CD4 arising during HIV infection will be investigated. The possible existence of molecular mimicry between autologous anti-CD4 antibodies and viral gpl2O will also be evaluated. From select individuals, anti-CD4 antibody producing lymphocytes will be used to generate combinatorial immunoglobulin expression libraries to clone and express the anti-CD4 antibodies. These recombinant Fab's will then be characterized structurally and mapped for binding to native and mutant CD4's. They will be analyzed for their ability to block different recombinant gpl2O's, and to inhibit viral infection in vitro. Structural information relevant to virus/CD4 interactions potentially useful for protection, immune intervention, and/or rational drug design will be obtained through these further molecular characterizations.