http://purl.uniprot.org/citations/17620420 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/17620420 | http://www.w3.org/2000/01/rdf-schema#comment | "ObjectiveCD8(+) T-cells specific for islet antigens are essential for the development of type 1 diabetes in the NOD mouse model of the disease. Such T-cells can also be detected in the blood of type 1 diabetic patients, suggesting their importance in the pathogenesis of the human disease as well. The development of peptide-based therapeutic reagents that target islet-reactive CD8(+) T-cells will require the identification of disease-relevant epitopes.Research design and methodsWe used islet-infiltrating CD8(+) T-cells from HLA-A*0201 transgenic NOD mice in an interferon-gamma enzyme-linked immunospot assay to identify autoantigenic peptides targeted during the spontaneous development of disease. We concentrated on insulin (Ins), which is a key target of the autoimmune response in NOD mice and patients alike.ResultsWe found that HLA-A*0201-restricted T-cells isolated from the islets of the transgenic mice were specific for Ins1 L3-11, Ins1 B5-14, and Ins1/2 A2-10. Insulin-reactive T-cells were present in the islets of mice as young as 5 weeks of age, suggesting an important function for these specificities early in the pathogenic process. Although there was individual variation in peptide reactivity, Ins1 B5-14 and Ins1/2 A2-10 were the immunodominant epitopes. Notably, in vivo cytotoxicity to cells bearing these peptides was observed, further confirming them as important targets of the pathogenic process.ConclusionsThe human versions of B5-14 and A2-10, differing from the murine peptides by only a single residue, represent excellent candidates to explore as CD8(+) T-cell targets in HLA-A*0201-positive type 1 diabetic patients."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.org/dc/terms/identifier | "doi:10.2337/db07-0332"xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "Yamada T."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "Marron M.P."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "Takaki T."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "DiLorenzo T.P."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "Serreze D.V."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "Baker J.C."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/author | "Jarchum I."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/name | "Diabetes"xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/pages | "2551-2560"xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/title | "In vivo cytotoxicity of insulin-specific CD8+ T-cells in HLA-A*0201 transgenic NOD mice."xsd:string |
http://purl.uniprot.org/citations/17620420 | http://purl.uniprot.org/core/volume | "56"xsd:string |
http://purl.uniprot.org/citations/17620420 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17620420 |
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