Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes

J Autoimmun. 2004 Aug;23(1):17-26. doi: 10.1016/j.jaut.2004.03.008.


Mice have two insulin genes that differ in the insulin sequence by two amino acids, including the B9 position. Given prior studies of the B:9-23 insulin peptide in NOD mice, a fundamental question is whether the immune response to the B:9-23 peptide of the two insulins is identical. We investigate responses to the immunization with B:9-23 insulin 1 and 2 peptides in NOD and RIP-B7.1 Balb/c mice. NOD and F1 (Balb/c x C57/Bl6) B7.1 transgenic mice were given either B:9-23 insulin 1, B:9-23 insulin 2 or tetanus toxoid (TT) control peptide. Insulin autoantibodies (IAA), and anti-B:9-23 antibodies (IgG1 and IgG2c) were measured. Subcutaneous injection of the insulin 2 but not the insulin 1 peptide significantly protected NOD mice from diabetes. Conceptually similar, insulin 1 peptide immunization accelerated diabetes in the B7.1 mice compared with insulin 2 peptide. Insulin 1 and 2 peptides induced similar levels of IAA in the NOD mice except at week 26, where insulin 2 induced higher levels of IAA. Anti-IgG1 B:9-23 peptide antibodies were higher in the insulin 2 immunized group of NOD mice, while IgG2c anti-B:9-23 peptide antibodies were higher in the insulin 1 group. Adoptive transfer of splenocytes from insulin 1 immunized mice to NOD.scid mice demonstrated accelerated diabetogenicity. The protection afforded by insulin 2 peptide but not insulin 1 peptide in the NOD mouse is reflected by its predominant Th2 humoral response. This may relate to the protection conferred by the insulin 1 knockout when bred onto NOD mice in contrast to acceleration of disease with an insulin 2 knockout.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / immunology
  • Insulin / immunology*
  • Insulin / metabolism*
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Peptide Fragments / immunology
  • Time Factors


  • Autoantibodies
  • B7-1 Antigen
  • Immunoglobulin G
  • Insulin
  • Peptide Fragments