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

C Daniel, B Weigmann, R Bronson… - Journal of Experimental …, 2011 - rupress.org
C Daniel, B Weigmann, R Bronson, H von Boehmer
Journal of Experimental Medicine, 2011rupress.org
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-Ag7 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 …
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-Ag7 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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