Anti-hormone anti-idiotypes are probes for receptor structure and function☆☆☆

A class of anti-idiotypes raised against antibodies specific for hormones or drugs would be anticipated to interact with their respective receptors. We have raised anti-TSH anti-idiotypic antibodies and found these to interact with the high affinity binding site for TSH on thyroid membranes, to induce 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 an Mr approximately 200,000 holoreceptor on protein blots of thyroid membranes resolved on SDS-PAGE in the absence of reductant. In another set of experiments we raised anti-idiotypic antibodies against monoclonal antibodies specific for the alpha and beta subunits of TSH, respectively. 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 compared to normal IgG and individual anti-idiotypes as well as mediating TSH-specific cAMP dependent physiologic changes. As a result of the second set of experiments, we propose that the interaction of TSH with its receptor involves two cooperative 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.