Immunotherapy with apitopes blocks the immune response to TSH receptor in HLA-DR transgenic mice

Research output: Contribution to journalArticle

Authors

  • Liselotte Jansson
  • Kathleen Vrolix
  • Andrea Jahraus
  • Keith F Martin

Colleges, School and Institutes

External organisations

  • Apitope International NV, Diepenbeek, Belgium.
  • Apitope Technology (Bristol) Ltd., Chepstow, United Kingdom.
  • Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.

Abstract

We have combined major histocompatibility complex-binding assays with immunization and tolerance induction experiments in HLA-DR3 transgenic mice to design apitopes (antigen-processing independent epitopes) derived from thyrotropin receptor (TSHR) for treatment of patients with Graves' disease (GD). A challenge model was created by using an adenovirus-expressing part of the extracellular domain of the thyrotropin receptor (TSHR289). This model was used to test whether current drug treatments for GD would have an impact on effective antigen-specific immunotherapy using the apitope approach. Furthermore, selected peptides were assessed for their antigenicity using peripheral blood mononuclear cell samples from patients with GD. A mixture of two immunodominant apitopes was sufficient to suppress both the T-cell and antibody response to TSHR when administered in soluble form to HLA-DR transgenic mice. Tolerance induction was not disrupted by current drug treatments. These results demonstrate that antigen-specific immunotherapy with apitopes from TSHR is a suitable approach for treatment of GD.

Details

Original languageEnglish
Pages (from-to)3446-3457
Number of pages12
JournalEndocrinology
Volume159
Issue number9
Early online date6 Aug 2018
Publication statusPublished - 1 Sep 2018