Epitopes described in "Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity."

Article Authors:Maki Nakayama; Joshua N Beilke; Jean M Jasinski; Masakazu Kobayashi; Dongmei Miao; Marcella Li; Marilyne G Coulombe; Edwin Liu; John F Elliott; Ronald G Gill; George S Eisenbarth
Article Title:Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity.
Reference Detail
Reference ID:1007430
Abstract:NOD mice with knockout of both native insulin genes and a mutated proinsulin transgene, alanine at position B16 in preproinsulin (B16:A-dKO mice), do not develop diabetes. Transplantation of NOD islets, but not bone marrow, expressing native insulin sequences (tyrosine at position B16) into B16:A-dKO mice rapidly restored development of insulin autoantibodies (IAAs) and insulitis, despite the recipients' pancreatic islets lacking native insulin sequences. Splenocytes from B16:A-dKO mice that received native insulin-positive islets induced diabetes when transferred into wild-type NOD/SCID or B16:A-dKO NOD/SCID mice. Splenocytes from mice immunized with native insulin B chain amino acids 9-23 (insulin B:9-23) peptide in CFA induced rapid diabetes upon transfer only in recipients expressing the native insulin B:9-23 sequence in their pancreata. Additionally, CD4(+) T cells from B16:A-dKO mice immunized with native insulin B:9-23 peptide promoted IAAs in NOD/SCID mice. These results indicate that the provision of native insulin B:9-23 sequences is sufficient to prime anti-insulin autoimmunity and that subsequent transfer of diabetes following peptide immunization requires native insulin B:9-23 expression in islets. Our findings demonstrate dependence on B16 alanine versus tyrosine of insulin B:9-23 for both the initial priming and the effector phase of NOD anti-islet autoimmunity.
Affiliations:Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center (UCHSC), Aurora, CO 80045-6511, USA.
Reference Type:Literature
PubMed ID:17607359
Journal:J Clin Invest
Journal Volume:117
Article Pages:1835-43
Journal ISSN:0021-9738
Article Chemical List:Autoantibodies;Insulin;Peptide Fragments;insulin B (9-23)
Article MeSH List:Animals; Autoantibodies(immunology); Autoimmunity(immunology); Bone Marrow Transplantation; CD4-Positive T-Lymphocytes(immunology; metabolism); Cell Transplantation; Cross-Priming(immunology); Diabetes Mellitus(genetics; immunology; metabolism; pathology); Immunization; Insulin(genetics; immunology; metabolism); Islets of Langerhans(immunology; metabolism); Mice; Mice, Inbred NOD; Peptide Fragments(genetics; immunology; metabolism); Spleen(immunology; metabolism; transplantation); Survival Rate
Curation Last Updated:2015-06-05 01:08:42