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

Roshini S. Abraham, S. Brian Wilson, Nelson F. De Souza, Jack L. Strominger, Stephen R. Munn, Chella S. David

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The major histocompatibility complex (MHC) genes play a significant role in the predisposition to insulin-dependent diabetes mellitus or type 1 diabetes. HLA-DQ8 (DQB1*0302, DQA1*0301) genes have been shown to have the highest relative risk for human type 1 diabetes. To develop a 'humanized' mouse model of diabetes, HLA-DQ8 was transgenically expressed in mice lacking endogenous class II genes. Since non-MHC background genes of the NOD influence the disease process, Aβ°/DQ8 mice were mated with the NOD strain and backcrossed to generate Aβ°/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 autoantigen 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 Aβ°/DQ8 and in the Aβ°/DQ8/NOD mice.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalHuman Immunology
Issue number7
StatePublished - Jul 1999


  • Antigen processing
  • GAD 65
  • MHC class II
  • Non-MHC genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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