| http://purl.uniprot.org/citations/27183389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27183389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27183389 | http://www.w3.org/2000/01/rdf-schema#comment | "The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide-major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I-restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key-like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci85679"xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci85679"xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Rizkallah P.J."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Rizkallah P.J."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Rossjohn J."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Rossjohn J."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Zhu C."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Zhu C."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Miles J.J."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Miles J.J."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Sewell A.K."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Sewell A.K."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Cole D.K."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Cole D.K."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Wooldridge L."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Wooldridge L."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Peakman M."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Peakman M."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Dolton G."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Dolton G."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Szomolay B."xsd:string |
| http://purl.uniprot.org/citations/27183389 | http://purl.uniprot.org/core/author | "Szomolay B."xsd:string |