The formation of thyrotropin receptor (TSHR) antibodies in a Graves' animal model requires the N-terminal segment of the TSHR extracellular domain

Endocrinology
S KikuokaH Niimi

Abstract

Immunization of AKR/N mice with murine fibroblasts, transfected with the TSH receptor (TSHR) and a murine major histocompatibility complex class II molecule having the same H-2k haplotype (but not either alone), induces immune thyroid disease with the humoral and histological features of human Graves', including the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs, which cause hyperthyroidism; and TSH-binding-inhibiting immunoglobulins. The primary functional epitope for both types of antibodies in Graves' patients is on the N-terminal portion of the extracellular domain of the TSHR, residues 25 to 165; most require residues 90-165 to express TSHRAb activity, as evidenced in studies using chimeras of the TSHR and lutropin-choriogonadotropin receptor (LH-CGR). To evaluate the role of this region of the TSHR in the formation of Graves' TSHRAbs, we immunized AKR/N mice with fibroblasts transfected with three human TSHR chimeras with residues 9-165 (Mc1+2), 90-165 (Mc2), or 261-370 (Mc4) substituted by equivalent residues of the rat LH-CGR. Mice immunized with the Mc1+2 and Mc2 chimeras, with the N-terminal portion of the extracellular domain of the TSHR substituted by LH-CGR residues, did not develop TSHRAb...Continue Reading

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Citations

Dec 13, 2003·Autoimmunity·Gattadahalli S Seetharamaiah
Jan 29, 2000·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·V KaczurC Balázs
Jan 4, 2007·Thyroid : Official Journal of the American Thyroid Association·Jane SandersBernard Rees Smith
Sep 15, 2018·Endocrine Reviews·Terry J Smith, Joseph A M J L Janssen
Dec 13, 2003·Endocrine Reviews·Bellur S PrabhakarTerry J Smith
Jul 14, 1998·The Journal of Clinical Endocrinology and Metabolism·J WortsmanL D Kohn
Dec 29, 2000·International Reviews of Immunology·L D KohnM Saji
Apr 14, 2005·Endocrine Reviews·Sandra M McLachlanBasil Rapoport
Sep 10, 1999·Journal of Autoimmunity·S A PatibandlaG S Seetharamaiah

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