CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope

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منابع مشابه

CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope.

The final pathway of beta cell destruction leading to insulin deficiency, hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that circulating CTLs can kill beta cells via recognition of a glucose-regulated epitope. First, we identified 2 naturally processed epitopes from the human preproinsulin signal peptide by elution from HLA-A2 (specifically, the protein encoded by the A*0...

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Circulating Preproinsulin Signal Peptide–Specific CD8 T Cells Restricted by the Susceptibility Molecule HLA-A24 Are Expanded at Onset of Type 1 Diabetes and Kill β-Cells

Type 1 diabetes results from T cell-mediated β-cell destruction. The HLA-A*24 class I gene confers significant risk of disease and early onset. We tested the hypothesis that HLA-A24 molecules on islet cells present preproinsulin (PPI) peptide epitopes to CD8 cytotoxic T cells (CTLs). Surrogate β-cell lines secreting proinsulin and expressing HLA-A24 were generated and their peptide ligandome ex...

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Designing a glycemic control strategy to maintain glucose homeostasis and prevent hypoglycemia for subjects with type 1 diabetes

This paper presents using the fractional PImDn controller module which manipulates insulin infusion rate to maintain normoglycemia in subjects with type 1 diabetes. To prevent severe hypoglycemia, a conventional proportional controller is used to regulate glucagon infusion rate when the blood glucose levels fall below a threshold. Two sets of controller parameters are obtained and evaluated. Fo...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2008

ISSN: 0021-9738

DOI: 10.1172/jci35449