NOD background genes influence T cell responses to GAD 65 in HLA-DQ8 transgenic mice

The major histocompatibility complex (MHC) genes play a significant: role i n the predisposition to insulin-dependent diabetes mellitus or type 1 diabe tes. HLA-DQ8 (DQB1*0302, DQA1*0301) genes have been shown to have the highe st relative risk for human type 1 diabetes. To develop a "humanized" mouse model of diabetes, HLA-DQ8 was transgenically expressed in mice lacking end ogenous class II genes. Since non-MHC background genes of the NOD influence the disease process, A beta degrees/DQ8 mice were mated with the NOD strai n and backcrossed to generate A beta degrees/DQ8/NOD mice. These mice have DQ8 as the sole MHC class II restriction element with NOD background genes at the N 2 generation. The DQ8 transgenic mice were used to identify T cell epitopes on glutamic acid decarboxylase (GAD 65), an important putative au toantigen in type 1 diabetes. The NOD background genes strongly influenced antigen processing, that is, different T cell epitopes were generated from the processing of GAD 65 in vivo in the A beta degrees/DQ8 and in the A bet a degrees/DQ8/NOD mice. Human Immunology 60, 583-590 (1999). (C) American S ociety for Histocompatibility and Immunogenetics, 1999. Published by Elsevi er Science Inc.