Anti-idiotypic antibodies as probes for hormone-receptor interaction.
On the premise that an antibody combining site is a mirror image of its antigen epitope, it is expected that an anti-idiotypic antibody (i.e., an antibody specific for the combining site of the first antibody) will be homologous to the epitope. Anti-idiotypic antibodies raised against hormones or drugs would, therefore, be anticipated to interact with their respective receptors. According to this schema, anti-idiotypic antibodies could either be antagonists or agonists. Most of the anti-idiotypic antibodies raised against hormones and neurotransmitters to date have proved, however, to be agonists. We have raised antithyrotropin (anti-TSH) anti-idiotypic antibodies and found these to interact with the high affinity binding site for TSH on thyroid plasma membranes and to induce cGMP-dependent adenylate cyclase activation and iodide transport into dispersed thyroid cells, as well as to promote their organization into follicular structures. The anti-TSH anti-idiotypic antibody interacted with a holoreceptor band of relative mass (Mr) approximately 200 000, resolved on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from thyroid membranes and transferred to nitrocellulose paper. In another set of experiments we raised anti-idiotypic antibodies against monoclonal antibodies specific, respectively, for the alpha and beta subunits of TSH. Neither the alpha nor beta monoclonal antibody specific anti-idiotypic antibodies interacted with the TSH holoreceptor. The combinations of the two anti-idiotypic antibodies, however, did so and increased basal cyclase activity significantly compared with normal immunoglobulin G. As a result of the second set of experiments, we propose that the interaction of TSH with its receptor involves two signals delivered by the two subunits rather than a single signal requiring their combination. Anti-idiotypic antibodies raised against highly purified hormones can be obtained in large amounts. They facilitate simple isolation of hormone receptors and are useful as probes for hormone-receptor interactions.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D000939:Epitopes / Q000032:analysis*; D006111:Graves Disease / Q000276:immunology; D006728:Hormones / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007130:Immunoglobulin Idiotypes; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011989:Receptors, Thyrotropin; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000276:immunology / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D000939:Epitopes; D006728:Hormones; D007130:Immunoglobulin Idiotypes; D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin; D013972:Thyrotropin