title: NOD background genes influence T cell responses to GAD 65 in HLA-DQ8 transgenic mice.
abstract: 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, DQA 1*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, AP"/DQ8 mice were mated with the NOD strain and backcrossed to generate Abeta degree/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 Abeta degree/DQ8 and in the Abeta degree/DQ8/NOD mice.
authors.affiliation: Department of Immunology, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Abraham
authors.forename: S B
authors.initials: SB
authors.lastname: Wilson
authors.forename: N F
authors.initials: NF
authors.lastname: de Souza
authors.forename: J L
authors.initials: JL
authors.lastname: Strominger
authors.forename: S R
authors.initials: SR
authors.lastname: Munn
authors.forename: C S
authors.initials: CS
authors.lastname: David
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D000949:Histocompatibility Antigens Class II; D005968:Glutamate Decarboxylase