DISCRETE CHARACTERISTICS OF ANTIBODIES RAISED AGAINST THYROTROPIN RECEPTOR-RELATED PEPTIDES WHOSE SEQUENCES ARE NOT CONSERVED IN THE LUTEINIZING-HORMONE CHORIONIC-GONADOTROPIN RECEPTOR

In order to identify the specific regions in the human TSH receptor fo r TSAb and thyroid stimulation-blocking antibody (TSBAb), we produced rabbit antibodies raised against several peptides of the extracellular domain of the human TSH receptor, where sequences are not conserved i n the LH/CG receptor, and measured the TSAb activity and TSBAb activit y of those antibodies using Chinese hamster ovary cells expressing hum an TSH receptors. Only antisera from rabbits that were immunized with a peptide of amino acid 32-56, including the small insertion near the N-terminal end of the extracellular domain, showed apparent TSAb activ ities and have been shown to be significantly precipitated by IgG of p atients with Graves' disease. TSAb, activity positively correlated wit h the antibody titers against the peptide in those rabbits. In contras t, antisera from rabbits immunized with a peptide of amino acid 352-37 8, including a part of the large insertion near the C-terminal end of the extracellular domain, showed the obvious TSBAb activities. TSBAb a ctivity also positively correlated with the degree of antibody titers against the peptide in those rabbits. Moreover, this peptide was signi ficantly immunoprecipitated by the IgG from hypothyroid patients who h ad TSBAb, and the immunoprecipitation of this peptide positively corre lated with TSBAb activities. These results suggest that the epitope re sponsible for TSAb is quite different from that for TSBAb in the extra cellular domain of the human TSH receptor.