A synthetic oligopeptide derived from human thyrotropin receptor sequence binds to Graves' immunoglobulin and inhibits thyroid stimulating antibody activity but lacks interactions with TSH

Mori, Toru; Sugawa, Hideo; Piraphatdist, T; Inoue, Daisuke; Enomoto, Tetsuya; Imura, Hiroo

doi:10.1016/0006-291x(91)91794-d

Cited by 56 publications

(22 citation statements)

References 16 publications

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“…On the other hand, a unique insertion area of the TSH receptor is reported through deletion mutants and chimeric studies to be insignificant for TSH binding and cAMP production by various ligand stimulations (12,14,16). As shown previously (10,14), binding of Graves' IgG to this particular area is relevant. In this study we showed almost complete absorption and recovery of TSAb and TBII from F-IgG by P-218 affinity chromatography.…”

Section: Discussionmentioning

confidence: 90%

“…353 to 363 of hTSH receptor, reduces TSAb activities of most Graves' IgG (10). We subsequently synthe¬ sized 13 peptides having the proximal sequence of P-195.…”

Section: Discussionmentioning

confidence: 99%

“…INTRODUCTION immunoglobulin (TBII), another TSH receptor antibody (9)(10)(11)(12)(13)(14)(15)(16)(17). Such complexity may be explained by TSH or autoanti-T is generally accepted THAT Graves' disease is caused by body recognition of three-dimensional structure of the receptor autoantibodies against the TSH receptor, especially thyroid- (18); however, there remains the possibility that serum IgG from stimulating antibody (TSAb) (1)(2)(3).…”

mentioning

confidence: 99%

“…P-262 has a completely reverse sequence of P-218 (354-367). These peptides were synthesized as described previously (9,10), and kept refrigerated as powders until use. All of these peptides were water-soluble and did not alter the pH of the solutions.…”

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confidence: 99%

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Immunoglobulin G That Interferes with Thyroid-Stimulating Antibody Measurements Can Be Eliminated Specifically by Incubation with Synthetic Peptides Corresponding to Partial Sequences of the Human Thyrotropin Receptor

Ueda¹,

Sugawa²,

Akamizu³

et al. 1993

Thyroid

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Two IgG preparations out of more than 100 tested, distinct from the typical Graves' disease IgG, were shown specifically to enhance the cAMP production of FRTL-5 cells by the addition of a synthetic peptide, P-218, corresponding to the partial amino acid sequence from No. 354 to 367 of the h thyroid-stimulating hormone (TSH) receptor. IgG obtained from a patient with Graves' disease revealed a serial alteration of the enhancement; negative in July, 1989, potent in January, 1991, and weak in September 1991. During this time there was no remarkable change in the patient's serum protein components or TSH receptor antibody activities. A peptide with a completely reverse sequence of P-218 showed little effect, and P-218 in combination with bTSH or forskolin did not affect cAMP production by these ligands, and did not alter the inhibitory activity of thyroid-stimulation-blocking antibody. High concentrations of P-218 resulted in reduction of such enhancing effects of cAMP by thyroid-stimulating antibody. P-218 affinity chromatography showed almost complete absorption and recovery of thyroid-stimulating antibody and P-218 reactivity. In the 15 synthesized peptides with proximal sequences of P-218 (from 338 to 378), regions thought to be involved with the enhancement were defined as follows: 354-367 (P-218) is a critical unit; 354-357 and 364-367 are considered to be the essential sites; several amino acid extensions on both N- and C-terminal sides of P-218 show additional enhancement. In conclusion, evidence was shown to indicate the presence of IgG that interferes with thyroid-stimulating antibody measurements.

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Section: Discussionmentioning

confidence: 90%

“…353 to 363 of hTSH receptor, reduces TSAb activities of most Graves' IgG (10). We subsequently synthe¬ sized 13 peptides having the proximal sequence of P-195.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Immunoglobulin G That Interferes with Thyroid-Stimulating Antibody Measurements Can Be Eliminated Specifically by Incubation with Synthetic Peptides Corresponding to Partial Sequences of the Human Thyrotropin Receptor

Ueda¹,

Sugawa²,

Akamizu³

et al. 1993

Thyroid

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“…(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56), no. 3 (52-71), no.…”

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confidence: 98%

Dissecting Linear and Conformational Epitopes on the Native Thyrotropin Receptor

Ando¹,

Latif²,

Daniel³

et al. 2004

Endocrinology

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The TSH receptor (TSHR) is the primary antigen in Graves' disease. In this condition, autoantibodies to the TSHR that have intrinsic thyroid-stimulating activity develop. We studied the epitopes on the native TSHR using polyclonal antisera and monoclonal antibodies (mAbs) derived from an Armenian hamster model of Graves' disease. Of 14 hamster mAbs analyzed, five were shown to bind to conformational epitopes including one mAb with potent thyroid-stimulating activity. Overlapping conformational epitopes were determined by cell-binding competition assays using fluorescently labeled mAbs. We identified two distinct conformational epitopes: epitope A for both stimulating and blocking mAbs and epitope B for only blocking mAbs. Examination of an additional three mouse-derived stimulating TSHR-mAbs also showed exclusive binding to epitope A. The remaining nine hamster-derived mAbs were neutral or low-affinity blocking antibodies that recognized linear epitopes within the TSHR cleaved region (residues 316-366) (epitope C). Serum from the immunized hamsters also recognized conformational epitopes A and B but, in addition, also contained high levels of TSHR-Abs interacting within the linear epitope C region. In summary, these studies indicated that the natively conformed TSHR had a restricted set of epitopes recognized by TSHR-mAbs and that the binding site for stimulating TSHR-Abs was highly conserved. However, high-affinity TSHR-blocking antibodies recognized two conformational epitopes, one of which was indistinguishable from the thyroid-stimulating epitope. Hence, TSHR-stimulating and blocking antibodies cannot be distinguished purely on the basis of their conformational epitope recognition.

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Pathogenesis of Autoimmune Thyroid Disease

Ajjan¹,

Weetman²

1999

Autoimmune Reactions

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A synthetic oligopeptide derived from human thyrotropin receptor sequence binds to Graves' immunoglobulin and inhibits thyroid stimulating antibody activity but lacks interactions with TSH

Cited by 56 publications

References 16 publications

Immunoglobulin G That Interferes with Thyroid-Stimulating Antibody Measurements Can Be Eliminated Specifically by Incubation with Synthetic Peptides Corresponding to Partial Sequences of the Human Thyrotropin Receptor

Immunoglobulin G That Interferes with Thyroid-Stimulating Antibody Measurements Can Be Eliminated Specifically by Incubation with Synthetic Peptides Corresponding to Partial Sequences of the Human Thyrotropin Receptor

Dissecting Linear and Conformational Epitopes on the Native Thyrotropin Receptor

Pathogenesis of Autoimmune Thyroid Disease

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