Human DQ8 can substitute for murine I-Ag7 in the selection of diabetogenic T cells restricted to I-Ag7

The Journal of Immunology : Official Journal of the American Association of Immunologists
Li WenConchi Mora

Abstract

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.

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Citations

May 13, 2006·Clinical Science·Yang Yang, Pere Santamaria
May 6, 2003·Current Diabetes Reports·Rohit N Kulkarni, Ariel Zisman
Jul 9, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miao WangDefu Zeng
Oct 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·John F ElliottKatherine M Kavanagh
Apr 28, 2006·International Immunology·Anthony QuinnEli Sercarz
Sep 15, 2007·International Immunology·Amy GardinerLynne S Arneson
Sep 17, 2003·The Journal of Clinical Investigation·Thomas StratmannLuc Teyton

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