Monoclonal antibodies to the thyrotropin receptor: implications for receptor structure and the action of autoantibodies in Graves disease.
Hybridoma cells have been obtained by fusing P3-NS1/1-Ag4-1 mouse myeloma cells with spleen cells from mice immunized with solubilized preparations of the thyrotropin receptor. Five clones were produced that secrete a monoclonal antibody whose binding to thyroid membranes is specifically inhibited by unlabeled thyrotropin. The antibody interacts with functioning thyroid cells in culture but not with nonfunctioning cells; this interaction is prevented by thyrotropin. The antibodies are capable of competitively blocking thyrotropin binding to bovine thyroid membrane preparations; they prevent 125I-labeled thyrotropin binding to a solubilized preparation of the glycoprotein component of the bovine thyrotropin receptor but are unable to inhibit 125I-labeled thyrotropin binding to liposomes containing gangliosides at comparable concentrations. They prevent 125I-labeled thyrotropin 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 thyrotropin-stimulated iodide uptake by functioning thyroid cells in culture.
D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D001323:Autoantibodies; D001667:Binding, Competitive; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D002999:Clone Cells; D006111:Graves Disease / Q000378:metabolism*; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology; D007700:Kinetics; D051379:Mice; D010954:Plasmacytoma; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011989:Receptors, Thyrotropin; D013154:Spleen / Q000276:immunology; D013972:Thyrotropin / Q000378:metabolism*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001323:Autoantibodies; D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D002772:Cholera Toxin