| http://purl.uniprot.org/citations/22522618 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22522618 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22522618 | http://www.w3.org/2000/01/rdf-schema#comment | "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 examined by mass spectrometry to discover naturally processed and HLA-A24-presented PPI epitopes. A novel PPI epitope was identified and used to generate HLA-A24 tetramers and examine the frequency of PPI-specific T cells in new-onset HLA-A*24(+) patients and control subjects. We identified a novel naturally processed and HLA-A24-presented PPI signal peptide epitope (PPI(3-11); LWMRLLPLL). HLA-A24 tetramer analysis reveals a significant expansion of PPI(3-11)-specific CD8 T cells in the blood of HLA-A*24(+) recent-onset patients compared with HLA-matched control subjects. Moreover, a patient-derived PPI(3-11)-specific CD8 T-cell clone shows a proinflammatory phenotype and kills surrogate β-cells and human HLA-A*24(+) islet cells in vitro. These results indicate that the type 1 diabetes susceptibility molecule HLA-A24 presents a naturally processed PPI signal peptide epitope. PPI-specific, HLA-A24-restricted CD8 T cells are expanded in patients with recent-onset disease. Human islet cells process and present PPI(3-11), rendering themselves targets for CTL-mediated killing."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.org/dc/terms/identifier | "doi:10.2337/db11-1520"xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.org/dc/terms/identifier | "doi:10.2337/db11-1520"xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "van Veelen P.A."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "van Veelen P.A."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Estorninho M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Estorninho M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Ellis R.J."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Ellis R.J."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Huang G.C."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Huang G.C."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Peakman M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Peakman M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Dayan C.M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Dayan C.M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Eichmann M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Eichmann M."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Kester M.G."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Kester M.G."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Knight R.R."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Knight R.R."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Kronenberg D."xsd:string |
| http://purl.uniprot.org/citations/22522618 | http://purl.uniprot.org/core/author | "Kronenberg D."xsd:string |