RRC ID 67376
Author Tahara K, Ban T, Minegishi T, Kohn LD.
Title Immunoglobulins from Graves' disease patients interact with different sites on TSH receptor/LH-CG receptor chimeras than either TSH or immunoglobulins from idiopathic myxedema patients.
Journal Biochem Biophys Res Commun
Abstract To examine the identity of binding sites for thyrotropin (TSH) and thyroid stimulating antibodies (TSAbs) associated with Graves' disease, we constructed eight human TSH receptor/rat LH-CG receptor chimeras. Substitution of amino acid residues 8-165 of the TSH receptor with the corresponding LH-CG receptor segment (Mc1 + 2) results in a chimera which retains high affinity TSH binding and the cAMP response to TSH but loses both the cAMP response to Graves' IgG and Graves' IgG inhibition of TSH binding. Two of three IgGs from idiopathic myxedema patients which contain thyroid stimulation blocking antibodies (TSBAbs) still, however, react with this chimera. Chimeras which substitute residues 90-165 (Mc2) and 261-370 (Mc4) retain the ability to interact with TSH, Graves' IgG, and idiopathic myxedema IgG. The data thus suggest that residues 8-165 contain an epitope specific for TSAbs and that TSH receptor determinants important for the activities of TSAbs and TSH are not identical. Further, binding sites for TSBAbs in idiopathic myxedema may be different from receptor binding sites for both Graves' IgG TSAb as well as TSH and may be different in individual patients.
Volume 179(1)
Pages 70-7
Published 1991-8-30
DOI 10.1016/0006-291x(91)91335-a
PII 0006-291X(91)91335-A
PMID 1883391
MeSH Base Sequence Chimera Cloning, Molecular DNA / genetics DNA / isolation & purification Graves Disease / immunology* Humans Immunoglobulins / metabolism* Kinetics Molecular Sequence Data Myxedema / immunology* Oligonucleotide Probes Receptors, LH / genetics Receptors, LH / immunology* Receptors, LH / metabolism Receptors, Thyrotropin / genetics Receptors, Thyrotropin / immunology* Receptors, Thyrotropin / metabolism Recombinant Proteins / immunology Recombinant Proteins / metabolism Restriction Mapping Thyrotropin / metabolism
IF 2.985
DNA material hTSHR (RDB06008) Mc2b (RDB05991) Mc1 (RDB05992) Mc1+2 (RDB05993) Mc1-4 (RDB05994) rLHR (RDB05995) Mc2a (RDB05996) MC124 (RDB05997) Mc1-3 (RDB05998) Mc2+4 (RDB05999) Mc234 (RDB06000) Mc3 (RDB06001) Mc2+3 (RDB06002) Mc2 (RDB06003) Rc2.45 (RDB06004) Mc1b (RDB06005) Mc1+2b (RDB06006) Mc4 (RDB06007)