title: A novel mouse model of Graves' disease: implications for a role of aberrant MHC class II expression in its pathogenesis.
abstract: Mice immunized with fibroblasts expressing an MHC class II molecule and human thyrotropin receptor (TSHR), but not either alone, develop major features characteristic of Graves' disease (GD), such as thyroid-stimulating autoantibodies directed against TSHR, increased serum thyroid hormone levels, and enlarged thyroid glands. The results indicate the need for the simultaneous expression of a class II molecule and the TSHR on the surface of the fibroblasts to develop stimulating anti-TSHR antibodies and full-blown GD in our model. A T cell line established from a mouse with hyperthyroidism proliferates in response to fibroblasts expressing a class II molecule and TSHR, but not to the fibroblasts expressing only TSHR, indicating that the class II molecules on the fibroblasts present TSHR-derived peptide(s) to T cells. These results strongly suggest that the acquisition of antigen-presenting ability by thyrocytes can lead to the induction or progression of GD. We identified a T cell epitope of TSHR by the proliferative response of spleen cells from mice immunized with fibroblasts expressing a class II molecule and TSHR to 80 overlapping peptides spanning the extracellular domain of human TSHR. The identification of a major T cell epitope provides an important clue to a novel therapy of GD.
authors: Department of Pediatrics, Chiba University School of Medicine, Japan. shimojo@pediat3.m.chiba-u.ac.jp
authors: N
authors: N
authors: Shimojo
authors: T
authors: T
authors: Arima
authors: K
authors: K
authors: Yamaguchi
authors: S
authors: S
authors: Kikuoka
authors: L D
authors: LD
authors: Kohn
authors: Y
authors: Y
authors: Kohno
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D006111:Graves Disease / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
chemical_list: D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin