| http://purl.uniprot.org/citations/25911099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25911099 | http://www.w3.org/2000/01/rdf-schema#comment | "Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new "humanized" model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142-161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142-161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142-161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142-161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142-161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS risk also from interisotypic combination between products of neighboring HLA-DR15 haplotype alleles, in this case the DQA1/DRB1 combination."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.641209"xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Eisenstein M."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Lassmann H."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Ben-Nun A."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Kaushansky N."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Hansen B.E."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Nielsen C.H."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Boura-Halfon S."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Milo R."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Altmann D.M."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/author | "Zeilig G."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/pages | "15260-15278"xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/title | "Role of a Novel Human Leukocyte Antigen-DQA1*01:02;DRB1*15:01 Mixed Isotype Heterodimer in the Pathogenesis of "Humanized" Multiple Sclerosis-like Disease."xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://purl.uniprot.org/core/volume | "290"xsd:string |
| http://purl.uniprot.org/citations/25911099 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25911099 |
| http://purl.uniprot.org/citations/25911099 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25911099 |
| http://purl.uniprot.org/uniprot/#_A0A0A7C3H3-mappedCitation-25911099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25911099 |
| http://purl.uniprot.org/uniprot/#_A0A0A7C3I1-mappedCitation-25911099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25911099 |
| http://purl.uniprot.org/uniprot/#_A0A0A0WDZ3-mappedCitation-25911099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25911099 |
| http://purl.uniprot.org/uniprot/#_A0A0E3DD60-mappedCitation-25911099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25911099 |
| http://purl.uniprot.org/uniprot/#_A0A0E3DD66-mappedCitation-25911099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25911099 |