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dc.contributor.authorLorente, Elena 
dc.contributor.authorRedondo-Anton, Jennifer 
dc.contributor.authorMartín-Esteban, Adrian
dc.contributor.authorGuasp, Pablo
dc.contributor.authorBarnea, Eilon
dc.contributor.authorLauzurica, Pilar 
dc.contributor.authorAdmon, Arie 
dc.contributor.authorLópez de Castro, José A
dc.date.accessioned2021-04-29T11:29:38Z
dc.date.available2021-04-29T11:29:38Z
dc.date.issued2019
dc.identifier.citationMol Cell Proteomics. 2019;18(11):2298-2309.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12830
dc.description.abstractHLA-B*40:02 is one of a few major histocompatibility complex class I (MHC-I) molecules associated with ankylosing spondylitis (AS) independently of HLA-B*27. The endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme that process MHC-I ligands and preferentially trims N-terminal basic residues, is also a risk factor for this disease. Like HLA-B*27 and other AS-associated MHC-I molecules, HLA-B*40:02 binds a relatively high percentage of peptides with ERAP2-susceptible residues. In this study, the effects of ERAP2 depletion on the HLA-B*40:02 peptidome were analyzed. ERAP2 protein expression was knocked out by CRISPR in the transfectant cell line C1R-B*40:02, and the differences between the peptidomes from the wild-type and ERAP2-KO cells were determined by label-free quantitative comparisons. The qualitative changes dependent on ERAP2 affected about 5% of the peptidome, but quantitative changes in peptide amounts were much more substantial, reflecting a significant influence of this enzyme on the generation/destruction balance of HLA-B*40:02 ligands. As in HLA-B*27, a major effect was on the frequencies of N-terminal residues. In this position, basic and small residues were increased, and aliphatic/aromatic ones decreased in the ERAP2 knockout. Other peptide positions were also affected. Because most of the non-B*27 MHC-I molecules associated with AS risk bind a relatively high percentage of peptides with N-terminal basic residues, we hypothesize that the non-epistatic association of ERAP2 with AS might be related to the processing of peptides with these residues, thus affecting the peptidomes of AS-associated MHC-I molecules.es_ES
dc.description.sponsorshipSupported by grants SAF2017/86578-R (Plan Nacional de I+D+i) to JALC, PI16CIII/00013 (Acción Estratégica de Salud) and S2018/BAA-4480 (Comunidad de Madrid) to PL, Israel Science Foundation, grant N. 1435/16 to AA, and an institutional grant of the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa. EL is a recipient of a Juan de la Cierva (FJCI-2016-28335) award from the Government of SPAIN.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAnkylosing Spondylitises_ES
dc.subjectERAP2es_ES
dc.subjectEnzyme Mechanismses_ES
dc.subjectHLA-B*40es_ES
dc.subjectImmunologyes_ES
dc.subjectInflammationes_ES
dc.subjectLabel-Free Quantificationes_ES
dc.subjectPeptidomicses_ES
dc.subject.meshAminopeptidases es_ES
dc.subject.meshCRISPR-Cas Systems es_ES
dc.subject.meshHLA-B Antigens es_ES
dc.subject.meshHLA-B27 Antigen es_ES
dc.subject.meshHumans es_ES
dc.subject.meshPeptide Fragments es_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshProteome es_ES
dc.subject.meshSpondylitis, Ankylosing es_ES
dc.titleSubstantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31530632es_ES
dc.format.volume18es_ES
dc.format.number11es_ES
dc.format.page2298-2309es_ES
dc.identifier.doi10.1074/mcp.RA119.001710es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderIsrael Science Foundationes_ES
dc.contributor.funderFundación Ramón Areceses_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1535-9484es_ES
dc.relation.publisherversionhttps://doi.org/10.1074/mcp.RA119.001710es_ES
dc.identifier.journalMolecular & cellular proteomicses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2017/86578-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16CIII/00013es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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