NEUROENDOCRINE (LHRH) RECEPTORS AND ANTI-IDIOTYPES

这里概述的项目使用了神经肽LHRH(黄体生成素 释放激素)作为阐明基础受体-配体的模型 互动。我们建议识别和映射的构象结构域 LHRH以分析分子识别和受体的机制 专一性。我们的实验是基于对免疫网络的研究 共享独特型，并测试假设，即 抗体分子和神经内分泌上存在的抗原反应区 在某些情况下，受体会彼此相似。这一结构 将使用反独特型来识别和操纵相似性 抗体，即针对LHRH识别产生的抗体 免疫球蛋白分子的结构。我们建议提出并测试这种情况 与LHRH垂体受体反应的抗独特型抗体和 系列单抗免疫抗LHRH免疫球蛋白的研究 抗LHRH抗体。我们将制备抗LHRH的单抗，并进行检测 它们与完整激素和化学修饰激素的结合专一性 类似物，评估这种抗体抑制的能力 激素受体结合，然后提纯和检测抗独特型抗体 识别受体中存在的特征结构域 互动。这项研究的结果将扩展免疫学的概念 共同独特型作为一种机制进入神经内分泌学领域 了解特定受体的相互作用。

The project outlined here used the neuropeptide LHRH (luteinizing hormone releasing hormone) as a model to illuminate basic receptor-ligand interactions. We propose to identify and map the conformational domains of LHRH in order to analyze mechanisms of molecular recognition and receptor specificity. Our experiments are based on studies of immunologic networks of shared idiotypy, and test the postulate that the conformation of antigen-reactive areas present on antibody molecules and on neuroendocrine receptors will, in some cases, be similar to each other. This structural similarity will be identified and manipulated using anti-idiotypic antibodies, that is, antibodies raised against the LHRH-recognition structure on immunoglobulin molecules. We propose to raise and test such antiidiotypic antibodies which react with LHRH pituitary receptors and anti-LHRH immunoglobulins by immunization with a series of monoclonal anti-LHRH antibodies. We will raise monoclonal anti-LHRH antibodies, assay their binding specificity on intact hormone and on chemically modified analogs, evaluate the ability of such antibodies to inhibit hormone-receptor binding, and then raise and assay antiidiotypic antibodies to identify characteristic structural domains present in receptor interactions. Results of this study will extend the immunologic concepts of shared idiotypy into the field of neuroendocrinology as a mechanism for understanding specific receptor interactions.