دورية أكاديمية
أعرض في EDS

Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis.

التفاصيل البيبلوغرافية
العنوان: Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis.
المؤلفون: Lorente, Elena, Redondo-Anton, Jennifer, Martín-Esteban, Adrian, Guasp, Pablo, Barnea, Eilon, Lauzurica, Pilar, Admon, Arie, López de Castro, José A
المساهمون: Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid (España), Israel Science Foundation, Fundación Ramón Areces
بيانات النشر: American Society for Biochemistry and Molecular Biology (ASBMB)
سنة النشر: 2019
المجموعة: REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII)
مصطلحات موضوعية: Ankylosing Spondylitis, ERAP2, Enzyme Mechanisms, HLA-B*40, Immunology, Inflammation, Label-Free Quantification, Peptidomics, Aminopeptidases, CRISPR-Cas Systems, HLA-B Antigens, HLA-B27 Antigen, Humans, Peptide Fragments, Protein Binding, Proteome, Spondylitis, Ankylosing
الوصف: 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. ; 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 ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 1535-9484
العلاقة: https://doi.org/10.1074/mcp.RA119.001710Test; info:eu-repo/grantAgreement/ES/SAF2017/86578-R; info:eu-repo/grantAgreement/ES/PI16CIII/00013; Mol Cell Proteomics. 2019;18(11):2298-2309.; http://hdl.handle.net/20.500.12105/12830Test; Molecular & cellular proteomics
DOI: 10.1074/mcp.RA119.001710
الإتاحة: https://doi.org/20.500.12105/12830Test
https://doi.org/10.1074/mcp.RA119.001710Test
https://hdl.handle.net/20.500.12105/12830Test
حقوق: http://creativecommons.org/licenses/by/4.0Test/ ; Atribución 4.0 Internacional ; open access
رقم الانضمام: edsbas.8A100519
قاعدة البيانات: BASE
الوصف
تدمد:15359484
DOI:10.1074/mcp.RA119.001710