New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models.
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.
Kong
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YC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit MI 48201, USA. ykong@med.wayne.edu
David
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CS
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
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D013954:Thyroglobulin