title: New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models.
abstract: H2 and HLA transgenes were utilized to clarify the role of class II genes in susceptibility to experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis (HT). Susceptibility was transferred by H2 class II transgenes to a resistant haplotype and by HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative Ab0 mice. Mice with a HLA-DRB1*1502 (DR2) transgene remain resistant to mouse thyroglobulin (mTg)-induced EAT, illustrating the role of HLA-DRB1 polymorphism. A role for HLA-DQ polymorphism was shown with hTg-induced EAT in HLA-DQ*0301/DQB1*0302 (DQ8), but not HLA-DQ*0103/DQB1*0601 (DQ6), transgenic mice. Yet, both DQ8+ and DQ6+ mice were unresponsive to mTg. Single transgenes obviate the problems from DR/DQ linkage disequilibrium and may distinguish the degree of susceptibility and the response to shared or specific epitopes. The introduction of conserved Eak transgene into Ab0 mice reveals a new role for H2E molecules in EAT. Without H2A molecules, EalphaEbetab molecules and T cells respond to hTg or pTg with severe thyroiditis, but not to mTg, thus distinguishing self from nonself. However, IAb genes in resistant mice ameliorate Eak transgene-mediated thyroiditis, similar to the effect of Eak transgene on IAs-mediated EAT. Studies in HLA DQ/DR double transgenic mice simulating human haplotypes could reveal HLA class II gene interactions in HT.
authors: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit MI 48201, USA. ykong@med.wayne.edu
authors: Y C
authors: YC
authors: Kong
authors: C S
authors: CS
authors: David
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D018014:Gene Transfer Techniques; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000503:physiopathology; D019076:Transgenes
chemical_list: D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D013954:Thyroglobulin