title: Immunization with an insulin peptide-MHC complex to prevent type 1 diabetes of NOD mice.
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.
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA. Li.Zhang@ucdenver.edu
authors: Li
authors: L
authors: Zhang
authors: Brian D
authors: BD
authors: Stadinski
authors: Aaron
authors: A
authors: Michels
authors: John W
authors: JW
authors: Kappler
authors: George S
authors: GS
authors: Eisenbarth
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007328:Insulin / Q000235:genetics* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology
chemical_list: D001324:Autoantigens; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; D007328:Insulin; D010446:Peptide Fragments; C097877:insulin B (9-23)