English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/124564
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
DC FieldValueLanguage
dc.contributor.authorÁlvarez, Iñaki-
dc.contributor.authorCarrascal, Montserrat-
dc.contributor.authorJaraquemada, Dolores-
dc.date.accessioned2015-11-05T13:12:24Z-
dc.date.available2015-11-05T13:12:24Z-
dc.date.issued2015-06-01-
dc.identifierdoi: 10.1016/j.jaut.2015.03.004-
dc.identifierissn: 1095-9157-
dc.identifier.citationJournal of Autoimmunity 60: 12-19 (2015)-
dc.identifier.urihttp://hdl.handle.net/10261/124564-
dc.descriptionIñaki Álvarez et al.-
dc.description.abstract© 2015 Elsevier Ltd. Promiscuous gene expression (pGE) of tissue-restricted self-antigens (TRA) in medullary thymic epithelial cells (mTECs) is in part driven by the Autoimmune Regulator gene (AIRE) and essential for self-tolerance. The link between AIRE functional mutations and multi-organ autoimmunity in human and mouse supports the role of pGE. Deep sequencing of the transcriptome revealed that mouse mTECs potentially transcribe an unprecedented range of >90% of all genes. Yet, it remains unclear to which extent these low-level transcripts are actually translated into proteins, processed and presented by thymic APCs to induce tolerance. To address this, we analyzed the HLA-DR-associated thymus peptidome. Within a large panel of peptides from abundant proteins, two TRA peptides were identified: prostate-specific semenogelin-1 (an autoantigen in autoimmune chronic prostatitis/chronic pelvic pain syndrome) and central nervous system-specific contactin-2 (an autoantigen in multiple sclerosis). Thymus expression of both genes was restricted to mTECs. SEMG1 expression was confined to mature HLA-DR<sup>hi</sup> mTECs of male and female donors and was AIRE-dependent, whereas CNTN2 was apparently AIRE-independent and was expressed by both populations of mTECs. Our findings establish a link between pGE, MHC-II peptide presentation and autoimmunity for bona fide human TRAs.-
dc.description.sponsorshipThis work was supported by The Spanish Ministry of Education SAF2009-08928 and SAF2012-35344 projects to DJ, project EME2006-26 of the UAB to IA, grant PI11-02479 of the Instituto Carlos III, Spanish Ministry of Health to RPB and by the Eurothymaide integrated project of the European Commission (LSHB-CT-2003-503410) to MG and BK and to RPB and DJ.-
dc.publisherAcademic Press-
dc.rightsclosedAccess-
dc.subjectPeptides-
dc.subjectAutoantigens-
dc.subjectTolerance-
dc.subjectThymus-
dc.subjectHuman-
dc.subjectMHC-
dc.titleCentral T cell tolerance: Identification of tissue-restricted autoantigens in the thymus HLA-DR peptidome-
dc.typeartículo-
dc.identifier.doi10.1016/j.jaut.2015.03.004-
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.jaut.2015.03.004-
dc.date.updated2015-11-05T13:12:24Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderMinisterio de Sanidad, Servicios Sociales e Igualdad (España)-
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)-
dc.contributor.funderEuropean Commission-
dc.contributor.funderInstituto de Salud Carlos III-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003751es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003176es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
Appears in Collections:(IIBB) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show simple item record
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.