Epitopes described in "Immunization with an insulin peptide-MHC complex to prevent type 1 diabetes of NOD mice."

Article Authors:Li Zhang; Brian D Stadinski; Aaron Michels; John W Kappler; George S Eisenbarth
Article Title:Immunization with an insulin peptide-MHC complex to prevent type 1 diabetes of NOD mice.
Reference Detail
Reference ID:1022560
Abstract:BACKGROUND: Mutating the insulin B:9-23 peptide prevents diabetes in NOD mice. Thus, the trimolecular complex of I-Ag7-insulin B:9-23 peptide-TCR may be essential for the development of spontaneous diabetes. Pathogenic T cells recognize the B:9-23 peptide presented by I-Ag7 in what is termed register 3, with the B22 basic amino acid (arginine) of the peptide bound in pocket 9 of I-Ag7. Our hypothesis is that immunization with an insulin B:12-22 peptide linked to I-Ag7 in register 3 (I-Ag7-B:RE#3 complex) can induce specific antibodies to the complex, block pathogenic TCRs, and thus prevent diabetes. METHODS: We immunized young NOD mice with recombinant I-Ag7-B:RE#3 protein, in which two amino acids of the peptide were mutated to fix the peptide in register 3, and investigated the induced antibodies targeted to the peptide in register 3. RESULTS: Specific antibodies targeting I-Ag7-B:RE#3 but not I-Ag7-HEL were identified in the sera of I-Ag7-B:RE#3 immunized mice. The sera inhibited B:9-23-induced T-cell responses in vitro. I-Ag7-B:RE#3 immunization delayed progression to diabetes (versus PBS, p=0.0005), while immunization with I-Ag7-HEL control complex did not. CONCLUSIONS: Immunization with I-Ag7-B:RE#3 complex significantly delays the development of insulin autoantibodies and the onset of diabetes in NOD mice, which is associated with the induction of I-Ag7-B:RE#3 antibodies.
Affiliations:Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA. Li.Zhang@ucdenver.edu
Reference Type:Literature
PubMed ID:22069260
Journal:Diabetes Metab Res Rev
Journal Volume:27
Article Pages:784-9
Journal ISSN:1520-7552
Article Chemical List:Autoantigens;HLA-DQ Antigens;HLA-DQ8 antigen;Histocompatibility Antigens Class II;I-A g7 antigen;Insulin;Peptide Fragments;insulin B (9-23)
Article MeSH List:Animals; Autoantigens(immunology); Diabetes Mellitus, Type 1(immunology; prevention & control); Female; HLA-DQ Antigens(immunology); Histocompatibility Antigens Class II(genetics; immunology); Insulin(genetics; immunology); Mice; Mice, Inbred NOD; Peptide Fragments(genetics; immunology)
Curation Last Updated:2015-07-30 20:43:53