Antigenic "Hot- Spots" on the TSH Receptor Hinge Region
Simeng Sun1, Sarawut Summachiwakij1, Ora Schneck1
1Thyroid Research Unit, Department of Medicine, James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Frontiers in Endocrinology
|January 23, 2019
Summary
The TSH receptor (TSHR) hinge region is an immunogenic target, with antibodies primarily binding to its carboxyl terminus. These TSHR antibodies may influence Graves' disease.
Area of Science:
- Endocrinology
- Immunology
- Molecular Biology
Background:
- The TSH receptor (TSHR) hinge region was historically viewed as a passive structural element.
- Recent studies reveal the hinge region functions as an extended hormone-binding site and is cleaved, separating the receptor into alpha and beta subunits.
- Monoclonal antibodies targeting the cleaved hinge region can induce thyroid cell apoptosis, suggesting its role in disease.
Purpose of the Study:
- To investigate the immunogenicity of the TSHR hinge region (aa280-410) by examining the antibody immune response after immunization.
- To identify specific antigenic targets within the TSHR hinge region.
Main Methods:
- Intense immunization of BALB/c mice with full-length TSHR cDNA.
- Analysis of antibody responses against the entire TSHR hinge region.
Main Results:
- TSHR hinge region antibodies were detected in 95% of immunized mice.
- Antibody responses were predominantly focused on residues 352-410, indicating novel antigenic "hotspots" in the carboxyl terminus.
- The immune response targeted more than just the cleaved portion of the hinge.
Conclusions:
- The TSHR hinge region contains an immunogenic pocket, particularly within its carboxyl terminus.
- These findings demonstrate the immunogenicity of the TSHR hinge region and its potential role in the heterogeneous immune response observed in Graves' disease.
- TSHR antibodies may actively contribute to the immune repertoire against the TSHR and influence disease phenotype.
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