Rabbit antibodies toward extracellular loops of the membrane spanning region of human thyrotropin receptor possess thyroid stimulating activities.
We have synthesized three different peptides, E1 (amino acid residues 478-497), E2 (amino acid residues 561-580) and E3 (amino acid residues 649-652), corresponding to the first, the second and the third extracellular loops of the membrane spanning region of human thyrotropin receptor (TSH-R), respectively. We have produced rabbit antibodies toward these peptides and evaluated their thyroid stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. Although only slight TSAb activity was observed in E1 antibodies, E2 and E3 antibodies possessed strong TSAb activities, the values of which were 1118% and 910%, respectively. None of these antibody had TBII activities. These results suggest that antibodies against the extracellular loops of the TSH-R can stimulate cAMP formation in thyroid cells and that these regions may be one of the candidates for the epitope against autoantibodies from patients with Graves' disease.
Endo
T
T
Third Department of Internal Medicine, University of Yamanashi Medical School, Japan.
Ohmori
M
M
Ikeda
M
M
Onaya
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008961:Models, Structural; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D011487:Protein Conformation; D011817:Rabbits / Q000276:immunology; D011989:Receptors, Thyrotropin / Q000276:immunology / Q000502:physiology*; D013961:Thyroid Gland / Q000187:drug effects*; D013972:Thyrotropin / Q000378:metabolism
D000906:Antibodies; D010455:Peptides; D011989:Receptors, Thyrotropin; D013972:Thyrotropin