Human DQ8 can substitute for murine I-Ag7 in the selection of diabetogenic T cells restricted to I-Ag7.
The strong association of type 1 diabetes with specific MHC class II genes, such as I-A(g7) in nonobese diabetic mice and HLA-DQ8 in humans, suggests that MHC class II molecules play an important role in the development of the disease. To test whether human DQ8 molecules could cross the species barrier and functionally replace their murine homolog I-A(g7), we generated DQ8/BDC2.5 transgenic mice. We have shown that BDC2.5 transgenic T cells are selected on DQ8 in the thymus and cause diabetes in a manner similar to that seen when the T cells are selected on H2(g7). Splenocytes from DQ8/BDC2.5 mice also showed reactivity toward islets in vitro as seen in H-2(g7)/BDC2.5 mice. We conclude that DQ8 molecules not only share structural similarity with the murine homolog I-A(g7), but also can cross the species barrier and functionally replace I-A(g7) molecules to stimulate diabetogenic T cells and produce diabetes.
Wen
Li
L
Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. li.wen@yale.edu
Wong
F Susan
FS
Sherwin
Robert
R
Mora
Conchi
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen