Abstract
Type 1 diabetes mellitus is strongly associated with HLA-DQ8 in humans and I-Ag7 in the NOD mouse. The disease is characterized by loss of tolerance to auto-antigens such as GAD, insulin, and the protein tyrosine phosphatase-like molecule, IA-2. We identified T cell epitopes on the intracytoplasmic region of IA-2 by immunizing DQ8/NOD, DQ8/B10, and NOD mice with overlapping 18 mer peptides in CFA. We identified four peptides presented both by DQ8 and NOD, five DQ8 specific peptides, and six NOD specific peptides. Both mouse lines failed to respond to ten peptides. We demonstrated MHC class II and CD4 restriction of proliferative responses using appropriate blocking antibodies. To understand the role of non-MHC genes in the generation of immune response to the islet auto-antigen, we evaluated cytokine secretion following immunization of DQ8 transgenic mice with strongly immunogenic peptides. The NOD background resulted in increased secretion of cytokines. In conclusion, we have identified IA-2 peptides that induce lymphoproliferative responses in DQ8 transgenic and NOD mice and shown that these peptides stimulate production of Th1 and Th2 cytokines.
Original language | English (US) |
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Pages (from-to) | 1099-1105 |
Number of pages | 7 |
Journal | Human Immunology |
Volume | 62 |
Issue number | 10 |
DOIs | |
State | Published - 2001 |
Keywords
- DQ8
- IA-2 epitopes
- NOD
- Transgenic
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology