[Anti-thyrotropin (TSH) receptor antibody binding epitopes of TSH receptor: site-directed mutagenesis approach]

Anti-TSH receptor antibodies are thought to be involved in the expression of autoimmune thyroid diseases, especially Graves' disease and idiopathic myxedema. Cloning of TSH receptor gene allowed us to study aspects of its structure and function at the molecular level, including autoantibody-binding sites. The long extracellular domain of TSH receptor was presumed to contain antibody-binding site. Site-directed mutagenesis of this domain defined regions important for autoantibodies. The C-terminal region of the extracellular domain, residues 295-306, 387-395 and tyrosine 385 were determinants of the "blocking-type" antibody, which were present in patients with primary hypothyroidism. And the N-terminal region, residues 34-37, 40, 42-45 and 52-56 were the site of the "stimulatory-type" antibody interactions, important in patients with Graves' disease.