{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:32:51Z","timestamp":1789410771238,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fundaci\u00f3n Ram\u00f3n Areces (institutional grant to the Centro de Biolog\u00eda Molecular Severo Ochoa)"},{"name":"Binational Science Foundation","award":["2009393"],"award-info":[{"award-number":["2009393"]}]},{"name":"Spanish Government (Plan Nacional de I+D+I)","award":["SAF2011\/25681"],"award-info":[{"award-number":["SAF2011\/25681"]}]},{"name":"Spanish Government (Plan Nacional de I+D+I)","award":["SAF2014\/51931-R"],"award-info":[{"award-number":["SAF2014\/51931-R"]}]},{"name":"Proteomics Unit of the Spanish National Biotechnology Centre is part of the Carlos III Networked Proteomics Platform, ProteoRed-PRB2"},{"name":"Carlos III Health Institute (ISCIII)","award":["PT13\/0001"],"award-info":[{"award-number":["PT13\/0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize the peptidome of the Beh\u00e7et's disease\u2013associated HLA\u2013B*51:01 allotype as well as the differential features of major peptide subsets and their distinct endoplasmic reticulum aminopeptidase 1 (ERAP\u20101)\u2013mediated processing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The endogenous B*51:01\u2010bound peptidome was characterized from 721.221 transfectant cells, after affinity chromatography and acid extraction, by tandem mass spectrometry. Recombinant ERAP\u20101 variants were used to digest synthetic B*51:01 ligands. HLA and transporter associated with antigen processing (TAP) binding affinities of peptide ligands were calculated with well\u2010established algorithms. ERAP\u20101 and ERAP\u20102 from 721.221 cells were characterized by genomic sequencing and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The B*51:01 peptidome consisted of 29.5% octamers, 61.7% nonamers, 4.8% decamers, and 4.0% longer peptides. The major peptide motif consisted of Pro and Ala at position 2, aliphatic\/aromatic position 3 residues, and Val and Ile at the C\u2010terminal position. The ligands with Pro or Ala at position 2 constituted 2 distinct subpeptidomes. Peptides with Pro at position 2 showed higher affinity for B*51:01 and lower affinity for TAP than those with Ala at position 2. Most important, both peptide subsets differed drastically in the susceptibility of their position 1 residues to ERAP\u20101, revealing a distinct influence of this enzyme on both subpeptidomes, which may alter their balance, affecting the global affinity of B*51:01\u2013peptide complexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:bold> ERAP\u20101 has a significant influence on the B*51:01 peptidome and its affinity.<\/jats:bold> <jats:bold>This influence is based on very distinct effects on the 2 subpeptidomes, whereby only peptides in the subpeptidome with Ala at position 2 are extensively destroyed, except when their position 1 residues are ERAP\u20101 resistant. This pattern provides a mechanism for the epistatic association of ERAP\u20101 and B*51:01 in Beh\u00e7et's disease.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39430","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T12:55:07Z","timestamp":1441976107000},"page":"505-515","source":"Crossref","is-referenced-by-count":60,"title":["The Peptidome of Beh\u00e7et's Disease\u2013Associated HLA\u2013B*51:01 Includes Two Subpeptidomes Differentially Shaped by Endoplasmic Reticulum Aminopeptidase 1"],"prefix":"10.1002","volume":"68","author":[{"given":"Pablo","family":"Guasp","sequence":"first","affiliation":[{"name":"CSIC, Centro de Biolog\u00eda Molecular Severo Ochoa Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Alvarez\u2010Navarro","sequence":"additional","affiliation":[{"name":"CSIC, Centro de Biolog\u00eda Molecular Severo Ochoa Madrid 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