Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes

Diabetes. 1999 Nov;48(11):2157-65. doi: 10.2337/diabetes.48.11.2157.


Two rodent models of autoimmune type 1 diabetes have been used to investigate the role of insulin as an autoantigen in this disease. In lymphopoenia-induced diabetes in the PVG.RT1u rat, neonatal tolerization with insulin B-chain peptides, but not A-chain peptides, conferred significant protection from disease. After rechallenge of adult rats, neonatally B-chain-tolerized animals showed diminished B-chain-specific T-cell proliferation, interleukin (IL)-2 production, and interferon-gamma (IFN-gamma) production, as compared with control animals. The epitope recognized by the PVG.RT1u rat was mapped to residues 1-18 of the B-chain; T-cell lines specific for this epitope were generated, and these conferred diabetes upon adoptive transfer to irradiated syngeneic recipients. In adult nonobese diabetic (NOD) mice, subcutaneous immunization with B-chain peptide 9-23 emulsified in incomplete Freund's adjuvant (IFA) was also potent at preventing onset of diabetes. In contrast to PVG.RT1u rats, NOD mice recognized an epitope within residues 10-29 of the insulin B-chain. The data implicate insulin as a target autoantigen in type 1 diabetes but do not support a role for molecular mimicry to insulin in the pathogenesis of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Epitopes / immunology
  • Epitopes / pharmacology
  • Immune Tolerance
  • Insulin / chemistry
  • Insulin / immunology
  • Insulin / pharmacology*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Mice
  • Mice, Inbred NOD
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology*
  • Thymectomy


  • Epitopes
  • Insulin
  • Interleukin-2
  • Peptide Fragments
  • Interferon-gamma