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+ populations were sorted from the LN and spleen of male mice. Post sort analysis of GFP vs. YFP (top row) and CD4 vs Foxp3 intracellular staining. (B) Schematic of the Foxp3 locus showing the TSDR amplified for CpG methylation analysis. The TATA box of the promoter is indicated, and Amp represents the region analyzed by bisulphite treatment, amplification(More)
In diabetic patients and susceptible mice, insulin is a targeted autoantigen. Insulin B chain 9-23 (B:9-23) autoreactive CD4 T cells are key for initiating autoimmune diabetes in NOD mice; however, little is known regarding their origin and function. To this end, B:9-23-specific, BDC12-4.1 T-cell receptor (TCR) transgenic (Tg) mice were studied, of which,(More)
A fundamental question about the pathogenesis of spontaneous autoimmune diabetes is whether there are primary autoantigens. For type 1 diabetes it is clear that multiple islet molecules are the target of autoimmunity in man and animal models. It is not clear whether any of the target molecules are essential for the destruction of islet beta cells. Here we(More)
Class II major histocompatibility molecules are the primary susceptibility locus for many autoimmune disorders, including type 1 diabetes. Human DQ8 and I-A(g7), in the NOD mouse model of spontaneous autoimmune diabetes, confers diabetes risk by modulating presentation of specific islet peptides in the thymus and periphery. We used an in silico molecular(More)
Autoreactive T cells infiltrating the target organ can possess a broad TCR affinity range. However, the extent to which such biophysical parameters contribute to T cell pathogenic potential remains unclear. In this study, we selected eight InsB9-23-specific TCRs cloned from CD4(+) islet-infiltrating T cells that possessed a relatively broad range of TCR(More)
There is accumulating evidence that autoimmunity to insulin B chain peptide, amino acids 9-23 (insulin B:9-23), is central to development of autoimmune diabetes of the NOD mouse model. We hypothesized that enhanced susceptibility to autoimmune diabetes is the result of targeting of insulin by a T-cell receptor (TCR) sequence commonly encoded in the(More)
OBJECTIVE To investigate the prevalence of beta-cell autoantigen-reactive peripheral T-cells in type 1 diabetes, we developed an immunoglobulin-free enzyme-linked immunospot (ELISPOT) assay and assessed its usefulness for diagnosing this disease. RESEARCH DESIGN AND METHODS Cellular immune responses to beta -cell autoantigens were studied both by(More)
We previously reported a peptide KS20 from islet amyloid polypeptide (IAPP) to be the target Ag for a highly diabetogenic CD4 T cell clone BDC-5.2.9. To track IAPP-reactive T cells in NOD mice and determine how they contribute to the pathogenesis of type 1 diabetes, we designed a new I-Ag7 tetramer with high affinity for BDC-5.2.9 that contains the peptide(More)
T he age of onset of type 1A diabetes is now im-munologically predictable (1). Either because of a lack of sufficient understanding of the patho-genesis of type 1A (immune-mediated) diabetes or a lack of effective therapeutics directed at relevant pathogenic pathways (or both), we cannot yet prevent this disease (2). The article by Liu et al. (3) in this(More)
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