Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes.
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.
Devendra
D
D
Barbara Davis Center for Childhood Diabetes, 4200 East 9th Avenue, Box B140, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Paronen
J
J
Moriyama
H
H
Miao
D
D
Eisenbarth
G S
GS
Liu
E
E
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007328:Insulin / Q000276:immunology* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D013997:Time Factors
D001323:Autoantibodies; D018122:B7-1 Antigen; D007074:Immunoglobulin G; D007328:Insulin; D010446:Peptide Fragments