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J Exp Med. 2011 Jul 4;208(7):1501-10. doi: 10.1084/jem.20110574. Epub 2011 Jun 20.

Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope.

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  • 1Laboratory of Lymphocyte Biology, Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA.

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.

PMID:
21690251
PMCID:
PMC3135372
DOI:
10.1084/jem.20110574
[PubMed - indexed for MEDLINE]
Free PMC Article
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