Epitopes described in "Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23)."

Article Authors:D Daniel; D R Wegmann
Article Title:Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23).
Reference Detail
Reference ID:1014331
Abstract:The observation that overt type I diabetes is often preceded by the appearance of insulin autoantibodies and the reports that prophylactic administration of insulin to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice, and human subjects results in protection from diabetes suggest that an immune response to insulin is involved in the process of beta cell destruction. We have recently reported that islet-infiltrating cells isolated from NOD mice are enriched for insulin-specific T cells, that insulin-specific T cell clones are capable of adoptive transfer of diabetes, and that epitopes present on residues 9-23 of the B chain appear to be dominant in this spontaneous response. In the experiments described in this report, the epitope specificity of 312 independently isolated insulin-specific T cell clones was determined and B-(9-23) was found to be dominant, with 93% of the clones exhibiting specificity toward this peptide and the remainder to an epitope on residues 7-21 of the A chain. On the basis of these observations, the effect of either subcutaneous or intranasal administration of B-(9-23) on the incidence of diabetes in NOD mice was determined. The results presented here indicate that both subcutaneous and intranasal administration of B-(9-23) resulted in a marked delay in the onset and a decrease in the incidence of diabetes relative to mice given the control peptide, tetanus toxin-(830-843). This protective effect is associated with reduced T-cell proliferative response to B-(9-23) in B-(9-23)-treated mice.
Reference Type:Literature
PubMed ID:8570667
Journal:Proc Natl Acad Sci U S A
Journal Volume:93
Article Pages:956-60
Journal ISSN:1091-6490
Article Chemical List:Epitopes;Immunodominant Epitopes;Insulin;Peptide Fragments;insulin B (9-23);Freund's Adjuvant
Article MeSH List:Administration, Intranasal; Amino Acid Sequence; Animals; Clone Cells; Diabetes Mellitus, Type 1(prevention & control); Epitopes; Female; Freund's Adjuvant; Immunodominant Epitopes; Immunotherapy, Active; Injections, Subcutaneous; Insulin(immunology; therapeutic use); Lymph Nodes(immunology); Lymphocyte Activation; Mice; Mice, Inbred NOD; Molecular Sequence Data; Peptide Fragments(immunology; therapeutic use); T-Lymphocytes(immunology)
Curation Last Updated:2015-07-30 20:29:30