Biologic activity of anti-thyrotropin anti-idiotypic antibody.

We raised an antihuman thyrotropin anti-idiotypic antibody and showed that it was active at the thyrotropin receptor. Thus this antibody inhibited 125I b-TSH binding to thyroid plasma membranes, stimulated adenylate cyclase activity through a guanyl nucleotide-dependent mechanism, increased radioiodide entry rate into isolated porcine thyroid follicular cells, and induced such cultured cells to organize into follicles. All these parameters are typical of thyrotropin action. This work raises the possibility that thyroid stimulating antibodies that cause the hyperthyroidism of Graves disease may be, at least in some patients, anti-thyrotropin anti-idiotypic antibodies. It also offers a novel method whereby antireceptor antibodies used in the isolation and characterization of the receptor may be raised from ligands.