| First Author | Devendra D | Year | 2004 |
| Journal | J Autoimmun | Volume | 23 |
| Issue | 1 | Pages | 17-26 |
| PubMed ID | 15236749 | Mgi Jnum | J:91669 |
| Mgi Id | MGI:3050170 | Doi | 10.1016/j.jaut.2004.03.008 |
| Citation | Devendra D, et al. (2004) Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes. J Autoimmun 23(1):17-26 |
| abstractText | 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/cxC57/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 (IgG(1) and IgG(2c)) 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-IgG(1) B:9-23 peptide antibodies were higher in the insulin 2 immunized group of NOD mice, while IgG(2c) 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. |
