Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 7, Pages 1501-1510Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110574
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Funding
- National Institutes of Health [AI-53102]
- BMBF-LPD [9901/8-184]
- Federal State of Hessen, Germany
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Type 1 diabetes (T1D) results from the destruction of insulin-secreting pancreatic. 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.
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