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 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.
Abraham
R S
RS
Department of Immunology, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Wilson
S B
SB
de Souza
N F
NF
Strominger
J L
JL
Munn
S R
SR
David
C S
CS
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*
D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D000949:Histocompatibility Antigens Class II; D005968:Glutamate Decarboxylase