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dc.contributor.authorLorente, Elena 
dc.contributor.authorInfantes, Susana 
dc.contributor.authorBarnea, Eilon
dc.contributor.authorBeer, Ilan
dc.contributor.authorGarcia, Ruth 
dc.contributor.authorLasala, Fatima
dc.contributor.authorJimenez, Mercedes 
dc.contributor.authorVilches, Carlos
dc.contributor.authorLemonnier, François A
dc.contributor.authorAdmon, Arie 
dc.contributor.authorLópez, Daniel
dc.identifier.citationJ Virol. 2012 Jan;86(1):527-41. doi: 10.1128/JVI.05737-11. Epub 2011 Oct 26.es_ES
dc.description.abstractThe transporter associated with antigen processing (TAP) delivers the viral proteolytic products generated by the proteasome in the cytosol to the endoplasmic reticulum lumen that are subsequently recognized by cytotoxic T lymphocytes (CTLs). However, several viral epitopes have been identified in TAP-deficient models. Using mass spectrometry to analyze complex human leukocyte antigen (HLA)-bound peptide pools isolated from large numbers of TAP-deficient vaccinia virus-infected cells, we identified 11 ligands naturally presented by four different HLA-A, HLA-B, and HLA-C class I molecules. Two of these ligands were presented by two different HLA class I alleles, and, as a result, 13 different HLA-peptide complexes were formed simultaneously in the same vaccinia virus-infected cells. In addition to the high-affinity ligands, one low-affinity peptide restricted by each of the HLA-A, HLA-B, and HLA-C class I molecules was identified. Both high- and low-affinity ligands generated long-term memory CTL responses to vaccinia virus in an HLA-A2-transgenic mouse model. The processing and presentation of two vaccinia virus-encoded HLA-A2-restricted antigens took place via proteasomal and nonproteasomal pathways, which were blocked in infected cells with chemical inhibitors specific for different subsets of metalloproteinases. These data have implications for the study of the effectiveness of early empirical vaccination with cowpox virus against smallpox disease.es_ES
dc.description.sponsorshipThis work was supported by grants to D.L. from the Programa Ramón y Cajal, Ministerio de Ciencia e Innovación and the FIPSE Foundation and to A.A. from the ISF 9916/05.es_ES
dc.publisherAmerican Society for Microbiologyes_ES
dc.relationinfo:eu-repo/grantAgreement/ES/ISF 9916/05es_ES
dc.subject.meshATP-Binding Cassette Transporters es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntigen Presentation es_ES
dc.subject.meshAntigen-Presenting Cells es_ES
dc.subject.meshCD8-Positive T-Lymphocytes es_ES
dc.subject.meshCell Line es_ES
dc.subject.meshHistocompatibility Antigens Class I es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLigands es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshVaccinia es_ES
dc.subject.meshVaccinia virus es_ES
dc.titleMultiple viral ligands naturally presented by different class I molecules in transporter antigen processing-deficient vaccinia virus-infected cellses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.identifier.journalJournal of virologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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