{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:26:52Z","timestamp":1789590412863,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Binational Science Foundation","award":["2009393"],"award-info":[{"award-number":["2009393"]}]},{"name":"Plan Nacional de I+D+i","award":["SAF2014\/51931-R"],"award-info":[{"award-number":["SAF2014\/51931-R"]}]},{"name":"Fundaci\u00f3n Ram\u00f3n Areces to the Centro de Biolog\u00eda Molecular Severo Ochoa"},{"name":"Spanish Government","award":["BES-2012-052113 and BES-2015-072729"],"award-info":[{"award-number":["BES-2012-052113 and BES-2015-072729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the influence of endoplasmic reticulum aminopeptidase 2 (ERAP\u20102) expression on the HLA\u2013B*27 peptidome in live cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using immunoaffinity chromatography and acid extraction, HLA\u2013B*27:05\u2013bound peptides were isolated from 2 ERAP\u20102\u2013negative lymphoblastoid cell lines and 1 ERAP\u20102\u2013positive lymphoblastoid cell line expressing functionally indistinguishable ERAP\u20101 variants. More than 2,000\u20134,000 B*27:05 ligands were identified from each cell line, and their relative abundance was established by quantitative tandem mass spectrometry and MaxQuant\u2010based peptide analyses. Pairwise comparisons were used to determine the structural features of peptides whose relative abundance was dependent on the presence of ERAP\u20102. Synthetic peptide digestions were performed with recombinant ERAP\u20101 and ERAP\u20102. Peptide affinity was estimated with standard algorithms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The B*27:05 peptidome from ERAP\u20102\u2013positive cells showed 3\u20134% fewer peptides with N\u2010terminal basic residues than did the peptidome from ERAP\u20102\u2013negative cells. Among the shared peptides, those most abundant in the presence of ERAP\u20102 included more nonamers, fewer decamers, and fewer N\u2010terminal basic residues than the peptides predominant in ERAP\u20102\u2013negative cells. These ERAP\u20102\u2013dependent changes did not alter the global affinity of the B*27:05 peptidome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ERAP\u20102 significantly influences the B*27:05\u2010bound peptidome by destroying some ligands and decreasing the abundance of many more ligands with N\u2010terminal basic residues, while increasing the abundance of nonamers. The former effects are best explained by direct ERAP\u20102 trimming. The effects on peptide length might be attributed to ERAP\u20102\u2013induced activation of ERAP\u20101 trimming. These data support the notion of a peptide\u2010mediated mechanism as the basis for the association of ERAP\u20102 with ankylosing spondylitis. Analogous effects on other major histocompatibility complex class I peptidomes might explain the involvement of ERAP\u20102 in HLA\u2013B27\u2013negative spondyloarthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39734","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T20:22:49Z","timestamp":1461615769000},"page":"2466-2475","source":"Crossref","is-referenced-by-count":44,"title":["Functional Interaction of the Ankylosing Spondylitis\u2013Associated Endoplasmic Reticulum Aminopeptidase 2 With the HLA\u2013B*27 Peptidome in Human Cells"],"prefix":"10.1002","volume":"68","author":[{"given":"Adrian","family":"Mart\u00edn\u2010Esteban","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (Consejo Superior de Investigaciones Cient\u00edficas and Universidad Aut\u00f3noma) Madrid 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molecular implicado en la configuraci\u00f3n del peptidoma de HLA\u2010B*27 por variantes naturales de ERAP1 asociadas a la espondilitis anquilosante. PhD Thesis. Universidad Aut\u00f3noma de Madrid; 2015."},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207467"},{"key":"e_1_2_7_42_1","first-page":"S268","article-title":"Functional implications of the endoplasmic reticulum aminopeptidase 2 (ERAP2) association with ankylosing spondylitis and Crohn's disease: impact on the unfolded protein response [abstract]","volume":"66","author":"Zhang Z","year":"2014","journal-title":"Arthritis Rheum"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199909)42:9<1975::AID-ANR25>3.0.CO;2-V"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39734","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:13:32Z","timestamp":1759940012000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,28]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1002\/art.39734"],"URL":"https:\/\/doi.org\/10.1002\/art.39734","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,28]]}}}