A Region on the Human Thyrotropin Receptor which can Induce Antibodies that Inhibit Thyrotropin-mediated Activation of in vitro Thyroid Cell Function also contains a Highly Immunogenic epitope

Johns S. Dallas, Gattadahalli S. Seetharamaiah, Samuel J. Cunningham, Randall M. Goldblum, Rajesh K. Desai, Bellur S. Prabhakar

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Autoantibodies to the thyrotropin receptor (TSHr) bind to the extracellular domain of the TSHr (ETSHr) and either stimulate of inhibit thyroid cell function and/or growth. In order to investigate the regulation and the specificity of the immune response to the TSHr, our laboratory recently produced recombinant human ETSHr protein by using the baculovirus expression system. In the present study, we used the recombinant ETSHr protein, a panel of overlapping synthetic peptides derived from the TSHr, and polyclonal rabbit antibodies produced against recombinant ETSHr and synthetic peptides to define a highly immunogenic region (aa 352-388) of the TSHr. Moreover, we used competitive inhibition studies to identify a dominant epitope (aa 367-372) within this region to which ETSHr antibodies react. This immunodominant epitope lies within a region unique to the TSHr when compared to the other glycoprotein hormone receptors. These data, together with the earlier observation that antibodies against aa region 357-372 can inhibit thyrotropin (TSH)-mediated activation of thyroid cells in culture, show that aa 367-372 represents, an immunodominant epitope within a functionally important region which is unique to the TSHr. Therefore, this region may play an important role in the induction or modulation of the specific immune response against the TSHr.

Original languageEnglish (US)
Pages (from-to)469-483
Number of pages15
JournalJournal of Autoimmunity
Volume7
Issue number4
DOIs
StatePublished - Aug 1994

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Thyrotropin Receptors
Thyrotropin
Epitopes
Immunodominant Epitopes
Thyroid Gland
Antibodies
Peptides
Baculoviridae
Autoantibodies
Glycoproteins
Cell Culture Techniques
Hormones
Rabbits
Growth
In Vitro Techniques
Protein Domains

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A Region on the Human Thyrotropin Receptor which can Induce Antibodies that Inhibit Thyrotropin-mediated Activation of in vitro Thyroid Cell Function also contains a Highly Immunogenic epitope. / Dallas, Johns S.; Seetharamaiah, Gattadahalli S.; Cunningham, Samuel J.; Goldblum, Randall M.; Desai, Rajesh K.; Prabhakar, Bellur S.

In: Journal of Autoimmunity, Vol. 7, No. 4, 08.1994, p. 469-483.

Research output: Contribution to journalArticle

Dallas, Johns S. ; Seetharamaiah, Gattadahalli S. ; Cunningham, Samuel J. ; Goldblum, Randall M. ; Desai, Rajesh K. ; Prabhakar, Bellur S. / A Region on the Human Thyrotropin Receptor which can Induce Antibodies that Inhibit Thyrotropin-mediated Activation of in vitro Thyroid Cell Function also contains a Highly Immunogenic epitope. In: Journal of Autoimmunity. 1994 ; Vol. 7, No. 4. pp. 469-483.
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abstract = "Autoantibodies to the thyrotropin receptor (TSHr) bind to the extracellular domain of the TSHr (ETSHr) and either stimulate of inhibit thyroid cell function and/or growth. In order to investigate the regulation and the specificity of the immune response to the TSHr, our laboratory recently produced recombinant human ETSHr protein by using the baculovirus expression system. In the present study, we used the recombinant ETSHr protein, a panel of overlapping synthetic peptides derived from the TSHr, and polyclonal rabbit antibodies produced against recombinant ETSHr and synthetic peptides to define a highly immunogenic region (aa 352-388) of the TSHr. Moreover, we used competitive inhibition studies to identify a dominant epitope (aa 367-372) within this region to which ETSHr antibodies react. This immunodominant epitope lies within a region unique to the TSHr when compared to the other glycoprotein hormone receptors. These data, together with the earlier observation that antibodies against aa region 357-372 can inhibit thyrotropin (TSH)-mediated activation of thyroid cells in culture, show that aa 367-372 represents, an immunodominant epitope within a functionally important region which is unique to the TSHr. Therefore, this region may play an important role in the induction or modulation of the specific immune response against the TSHr.",
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