Monoclonal antiidiotypic antibodies interact with the 93 kilodalton thyrotropin receptor and exhibit heterogeneous biological activities.
Ten antiidiotypic monoclonal antibodies (AI mAb) reacting with the TSH receptor were produced by immunization of mice with a mouse mAb directed to a TSH epitope involved in the binding of the hormone to the receptor. The AI mAb were tested for their effects on the TSH receptor-adenylate cyclase system. Four AI mAb behave as agonists of TSH as they compete with TSH for binding to the receptor and stimulate the adenylate cyclase activity. Five AI mAb inhibited both TSH binding to the receptor and adenylate cyclase activity in the presence and absence of TSH; they were thus considered as antagonists of the hormone. One mAb inhibited only slightly the binding of TSH to the receptor and did not interfere significantly with the adenylate cyclase activity. The 10 AI mAb bound with various apparent affinities to solubilized thyroid membrane proteins but not to kidney, spleen, and liver membranes. Membrane desialylation did not significantly alter the binding of the AI mAb whereas deglycosylation modified more or less strongly the binding of mAb to thyroid membranes. It was also shown that the binding to solubilized thyroid membranes of the 10 mAb was inhibited by anti-TSH receptor autoantibodies present in patients with autoimmune disease. The mAb were further analyzed by Western blot analysis. One mAb did not react with the antigen, which suggested that it was directed to a conformational epitope. The other 9 mAb reacted with a protein of 70 kilodaltons and 5 revealed another band of 93 kilodaltons in accordance with the TSH receptor size deduced from the recently molecular cloning.
Costagliola
S
S
U38 INSERM, Marseille, France.
Ruf
J
J
Durand-Gorde
M J
MJ
Carayon
P
P
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000502:physiology; D001323:Autoantibodies / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007668:Kidney / Q000276:immunology; D008099:Liver / Q000276:immunology; D008566:Membranes / Q000276:immunology; D051379:Mice; D008970:Molecular Weight; D011989:Receptors, Thyrotropin / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D011989:Receptors, Thyrotropin; D000262:Adenylyl Cyclases