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 for 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 in the LH/CG receptor, and measured the TSAb activity and TSBAb activity of those antibodies using Chinese hamster ovary cells expressing human 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 activities and have been shown to be significantly precipitated by IgG of patients with Graves' disease. TSAb activity positively correlated with the antibody titers against the peptide in those rabbits. In contrast, antisera from rabbits immunized with a peptide of amino acid 352-378, including a part of the large insertion near the C-terminal end of the extracellular domain, showed the obvious TSBAb activities. TSBAb activity also positively correlated with the degree of antibody titers against the peptide in those rabbits. Moreover, this peptide was significantly immunoprecipitated by the IgG from hypothyroid patients who had TSBAb, and the immunoprecipitation of this peptide positively correlated with TSBAb activities. These results suggest that the epitope responsible for TSAb is quite different from that for TSBAb in the extracellular domain of the human TSH receptor.
Murakami
M
M
First Department of Internal Medicine, Gunma University School of Medicine, Gunma University, Maebashi, Japan.
Miyashita
K
K
Mizuma
H
H
Yamada
M
M
Iriuchijima
T
T
Takeuchi
T
T
Mori
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D019138:Antibodies, Blocking / Q000276:immunology; D016466:CHO Cells; D017124:Conserved Sequence; D006224:Cricetinae; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating / Q000276:immunology; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011974:Receptors, LH / Q000737:chemistry*; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000906:Antibodies; D019138:Antibodies, Blocking; D000939:Epitopes; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D010446:Peptide Fragments; D011974:Receptors, LH; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins