title: Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope.
abstract: Type 1 diabetes (T1D) results from the destruction of insulin-secreting pancreatic β cells by autoreactive T cells. Insulin is an essential target of the autoimmune attack. Insulin epitopes recognized by diabetogenic T cell clones bind poorly to the class II I-A(g7) molecules of nonobese diabetic (NOD) mice, which results in weak agonistic activity of the peptide MHC complex. Here, we describe a strongly agonistic insulin mimetope that effectively converts naive T cells into Foxp3(+) regulatory T cells in vivo, thereby completely preventing T1D in NOD mice. In contrast, natural insulin epitopes are ineffective. Subimmunogenic vaccination with strongly agonistic insulin mimetopes might represent a novel strategy to prevent T1D in humans at risk for the disease.
authors.affiliation: Laboratory of Lymphocyte Biology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Carolin
authors.initials: C
authors.lastname: Daniel
authors.forename: Benno
authors.initials: B
authors.lastname: Weigmann
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007328:Insulin / Q000819:agonists* / Q000276:immunology*; D007330:Insulin Antibodies / Q000097:blood; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007328:Insulin; D007330:Insulin Antibodies; D014612:Vaccines