{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:56:37Z","timestamp":1786989397192,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Ceschina","award":["000301_18_PE_SORRENTINO_FIORILLO"],"award-info":[{"award-number":["000301_18_PE_SORRENTINO_FIORILLO"]}]},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["000301_19_RS__SORRENTINO"],"award-info":[{"award-number":["000301_19_RS__SORRENTINO"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["000301_19_RS__FIORILLO"],"award-info":[{"award-number":["000301_19_RS__FIORILLO"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The strong association with the Major Histocompatibility Complex (MHC) class I genes represents a shared trait for a group of autoimmune\/autoinflammatory disorders having in common immunopathogenetic basis as well as clinical features. Accordingly, the main risk factors for Ankylosing Spondylitis (AS), prototype of the Spondyloarthropathies (SpA), the Beh\u00e7et\u2019s disease (BD), the Psoriasis (Ps) and the Birdshot Chorioretinopathy (BSCR) are HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02, respectively. Despite the strength of the association, the HLA pathogenetic role in these diseases is far from being thoroughly understood. Furthermore, Genome-Wide Association Studies (GWAS) have highlighted other important susceptibility factors such as Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and, less frequently, ERAP2 that refine the peptidome presented by HLA class I molecules to CD8+ T cells. Mass spectrometry analysis provided considerable knowledge of HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02 immunopeptidome. However, the combined effect of several ERAP1 and ERAP2 allelic variants could generate an altered pool of peptides accounting for the \u201cmis-immunopeptidome\u201d that ranges from suboptimal to pathogenetic\/harmful peptides able to induce non-canonical or autoreactive CD8+ T responses, activation of NK cells and\/or garbling the classical functions of the HLA class I molecules. This review will focus on this class of epitopes as possible elicitors of atypical\/harmful immune responses which can contribute to the pathogenesis of chronic inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms21249608","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"9608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Impact of the \u2018Mis-Peptidome\u2019 on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response"],"prefix":"10.3390","volume":"21","author":[{"given":"Valentina","family":"Tedeschi","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Paldino","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-452X","authenticated-orcid":false,"given":"Fabiana","family":"Paladini","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Mattorre","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9056-4077","authenticated-orcid":false,"given":"Loretta","family":"Tuosto","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"},{"name":"Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6859-5851","authenticated-orcid":false,"given":"Maria Teresa","family":"Fiorillo","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u2018Charles Darwin\u2019, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1399-0039.2010.01550.x","article-title":"The cell biology of major histocompatibility complex class I assembly: Towards a molecular understanding","volume":"76","author":"James","year":"2010","journal-title":"Tissue Antigens"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.humimm.2019.01.003","article-title":"Peptide trimming by endoplasmic reticulum aminopeptidases: Role of MHC class I binding and ERAP dimerization","volume":"80","author":"Evnouchidou","year":"2019","journal-title":"Hum. 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