dc.contributor.author | Lorente, Elena | |
dc.contributor.author | Redondo-Anton, Jennifer | |
dc.contributor.author | Martín-Esteban, Adrian | |
dc.contributor.author | Guasp, Pablo | |
dc.contributor.author | Barnea, Eilon | |
dc.contributor.author | Lauzurica, Pilar | |
dc.contributor.author | Admon, Arie | |
dc.contributor.author | López de Castro, José A | |
dc.date.accessioned | 2021-04-29T11:29:38Z | |
dc.date.available | 2021-04-29T11:29:38Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Mol Cell Proteomics. 2019;18(11):2298-2309. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/12830 | |
dc.description.abstract | HLA-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.sponsorship | Supported 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.iso | eng | es_ES |
dc.publisher | American Society for Biochemistry and Molecular Biology (ASBMB) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Ankylosing Spondylitis | es_ES |
dc.subject | ERAP2 | es_ES |
dc.subject | Enzyme Mechanisms | es_ES |
dc.subject | HLA-B*40 | es_ES |
dc.subject | Immunology | es_ES |
dc.subject | Inflammation | es_ES |
dc.subject | Label-Free Quantification | es_ES |
dc.subject | Peptidomics | es_ES |
dc.subject.mesh | Aminopeptidases | es_ES |
dc.subject.mesh | CRISPR-Cas Systems | es_ES |
dc.subject.mesh | HLA-B Antigens | es_ES |
dc.subject.mesh | HLA-B27 Antigen | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Peptide Fragments | es_ES |
dc.subject.mesh | Protein Binding | es_ES |
dc.subject.mesh | Proteome | es_ES |
dc.subject.mesh | Spondylitis, Ankylosing | es_ES |
dc.title | Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 31530632 | es_ES |
dc.format.volume | 18 | es_ES |
dc.format.number | 11 | es_ES |
dc.format.page | 2298-2309 | es_ES |
dc.identifier.doi | 10.1074/mcp.RA119.001710 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Israel Science Foundation | |
dc.contributor.funder | Fundación Ramón Areces | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1535-9484 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1074/mcp.RA119.001710 | es_ES |
dc.identifier.journal | Molecular & cellular proteomics | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2017/86578-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI16CIII/00013 | es_ES |
dc.rights.accessRights | open access | es_ES |