Monoclonal antibodies to the thyrotropin receptor: implications for receptor structure and the action of autoantibodies in Graves disease.

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Abstract
Hybridoma cells were obtained by fusing P3-NS1/1-Ag4-1 mouse myeloma cells with spleen cells from mice immunized with solubilized preparations of the thyrotropin [TSH] receptor. Five clones were produced that secrete a monoclonal antibody, the binding of which thyroid membranes is specifically inhibited by unlabeled TSH. The antibody interacts with functioning thyroid cells in culture but not with nonfunctioning cells; this interaction is prevented by TSH. The antibodies are capable of competitively blocking TSH binding to bovine thyroid membrane preparations; they prevent 125I-labeled TSH binding to a solubilized preparation of the glycoprotein component of the bovine TSH receptor, but are unable to inhibit 125I-labeled TSH binding to liposomes containing gangliosides at comparable concentrations. They prevent 125I-labeled TSH binding to rat, bovine or human (Graves disease) thyroid membrane preparations. They do not stimulate adenylate cyclase activity in thyroid membrane preparations but can inhibit TSH-stimulated iodide uptake by functioning thyroid cells in culture.