NEUROENDOCRINE (LHRH) RECEPTORS AND ANTI-IDIOTYPES

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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.