ERAP1 allotypes shape the epitope repertoire of virus-specific CD8+ T cell responses in acute hepatitis C virus infection
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Auteurs : Janine Kemming [Allemagne] ; Emma Reeves [Royaume-Uni] ; Katja Nitschke [Allemagne] ; Vanessa Widmeier [Allemagne] ; Florian Emmerich [Allemagne] ; Tobias Hermle [Allemagne] ; Emma Gostick [Royaume-Uni] ; Andreas Walker [Allemagne] ; Jörg Timm [Allemagne] ; David A. Price [Royaume-Uni] ; Maike Hofmann [Allemagne] ; Robert Thimme [Allemagne] ; Edward James [Royaume-Uni] ; Christoph Neumann-Haefelin [Allemagne]Source :
- Journal of Hepatology [ 0168-8278 ] ; 2019.
Abstract
Url:
DOI: 10.1016/j.jhep.2019.01.034
PubMed: 30769005
PubMed Central: 6527866
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ERAP1 allotypes shape the epitope repertoire of virus-specific CD8<sup>+</sup> T cell responses in acute hepatitis C virus infection</title><author><name sortKey="Kemming, Janine" sort="Kemming, Janine" uniqKey="Kemming J" first="Janine" last="Kemming">Janine Kemming</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af010">Faculty of Biology, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Faculty of Biology, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Reeves, Emma" sort="Reeves, Emma" uniqKey="Reeves E" first="Emma" last="Reeves">Emma Reeves</name><affiliation wicri:level="1"><nlm:aff id="af015">Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton</wicri:regionArea></affiliation></author><author><name sortKey="Nitschke, Katja" sort="Nitschke, Katja" uniqKey="Nitschke K" first="Katja" last="Nitschke">Katja Nitschke</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Widmeier, Vanessa" sort="Widmeier, Vanessa" uniqKey="Widmeier V" first="Vanessa" last="Widmeier">Vanessa Widmeier</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Emmerich, Florian" sort="Emmerich, Florian" uniqKey="Emmerich F" first="Florian" last="Emmerich">Florian Emmerich</name><affiliation wicri:level="1"><nlm:aff id="af020">Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Hermle, Tobias" sort="Hermle, Tobias" uniqKey="Hermle T" first="Tobias" last="Hermle">Tobias Hermle</name><affiliation wicri:level="1"><nlm:aff id="af025">Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation wicri:level="1"><nlm:aff id="af030">Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Walker, Andreas" sort="Walker, Andreas" uniqKey="Walker A" first="Andreas" last="Walker">Andreas Walker</name><affiliation wicri:level="1"><nlm:aff id="af035">Institute for Virology, Heinrich Heine University, Düsseldorf, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea></affiliation></author><author><name sortKey="Timm, Jorg" sort="Timm, Jorg" uniqKey="Timm J" first="Jörg" last="Timm">Jörg Timm</name><affiliation wicri:level="1"><nlm:aff id="af035">Institute for Virology, Heinrich Heine University, Düsseldorf, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation wicri:level="1"><nlm:aff id="af030">Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Hofmann, Maike" sort="Hofmann, Maike" uniqKey="Hofmann M" first="Maike" last="Hofmann">Maike Hofmann</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Thimme, Robert" sort="Thimme, Robert" uniqKey="Thimme R" first="Robert" last="Thimme">Robert Thimme</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="James, Edward" sort="James, Edward" uniqKey="James E" first="Edward" last="James">Edward James</name><affiliation wicri:level="1"><nlm:aff id="af015">Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton</wicri:regionArea></affiliation></author><author><name sortKey="Neumann Haefelin, Christoph" sort="Neumann Haefelin, Christoph" uniqKey="Neumann Haefelin C" first="Christoph" last="Neumann-Haefelin">Christoph Neumann-Haefelin</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30769005</idno><idno type="pmc">6527866</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527866</idno><idno type="RBID">PMC:6527866</idno><idno type="doi">10.1016/j.jhep.2019.01.034</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000E10</idno><idno type="wicri:explorRef" wicri:stream="Pmc" 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id="af010">Faculty of Biology, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Faculty of Biology, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Reeves, Emma" sort="Reeves, Emma" uniqKey="Reeves E" first="Emma" last="Reeves">Emma Reeves</name><affiliation wicri:level="1"><nlm:aff id="af015">Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton</wicri:regionArea></affiliation></author><author><name sortKey="Nitschke, Katja" sort="Nitschke, Katja" uniqKey="Nitschke K" first="Katja" last="Nitschke">Katja Nitschke</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Widmeier, Vanessa" sort="Widmeier, Vanessa" uniqKey="Widmeier V" first="Vanessa" last="Widmeier">Vanessa Widmeier</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Emmerich, Florian" sort="Emmerich, Florian" uniqKey="Emmerich F" first="Florian" last="Emmerich">Florian Emmerich</name><affiliation wicri:level="1"><nlm:aff id="af020">Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Hermle, Tobias" sort="Hermle, Tobias" uniqKey="Hermle T" first="Tobias" last="Hermle">Tobias Hermle</name><affiliation wicri:level="1"><nlm:aff id="af025">Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation wicri:level="1"><nlm:aff id="af030">Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Walker, Andreas" sort="Walker, Andreas" uniqKey="Walker A" first="Andreas" last="Walker">Andreas Walker</name><affiliation wicri:level="1"><nlm:aff id="af035">Institute for Virology, Heinrich Heine University, Düsseldorf, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea></affiliation></author><author><name sortKey="Timm, Jorg" sort="Timm, Jorg" uniqKey="Timm J" first="Jörg" last="Timm">Jörg Timm</name><affiliation wicri:level="1"><nlm:aff id="af035">Institute for Virology, Heinrich Heine University, Düsseldorf, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation wicri:level="1"><nlm:aff id="af030">Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea></affiliation></author><author><name sortKey="Hofmann, Maike" sort="Hofmann, Maike" uniqKey="Hofmann M" first="Maike" last="Hofmann">Maike Hofmann</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Thimme, Robert" sort="Thimme, Robert" uniqKey="Thimme R" first="Robert" last="Thimme">Robert Thimme</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="James, Edward" sort="James, Edward" uniqKey="James E" first="Edward" last="James">Edward James</name><affiliation wicri:level="1"><nlm:aff id="af015">Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton</wicri:regionArea></affiliation></author><author><name sortKey="Neumann Haefelin, Christoph" sort="Neumann Haefelin, Christoph" uniqKey="Neumann Haefelin C" first="Christoph" last="Neumann-Haefelin">Christoph Neumann-Haefelin</name><affiliation wicri:level="1"><nlm:aff id="af005">Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Hepatology</title><idno type="ISSN">0168-8278</idno><idno type="eISSN">1600-0641</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Graphical abstract</title><fig id="f0030" position="anchor"><graphic xlink:href="ga1"></graphic></fig></div></front><back><div1 type="bibliography"><listBibl></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Hepatol</journal-id><journal-id journal-id-type="iso-abbrev">J. Hepatol</journal-id><journal-title-group><journal-title>Journal of Hepatology</journal-title></journal-title-group><issn pub-type="ppub">0168-8278</issn><issn pub-type="epub">1600-0641</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30769005</article-id><article-id pub-id-type="pmc">6527866</article-id><article-id pub-id-type="publisher-id">S0168-8278(19)30111-4</article-id><article-id pub-id-type="doi">10.1016/j.jhep.2019.01.034</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>ERAP1 allotypes shape the epitope repertoire of virus-specific CD8<sup>+</sup> T cell responses in acute hepatitis C virus infection</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kemming</surname><given-names>Janine</given-names></name><xref rid="af005" ref-type="aff">1</xref><xref rid="af010" ref-type="aff">2</xref><xref rid="fn1" ref-type="fn">†</xref></contrib><contrib contrib-type="author"><name><surname>Reeves</surname><given-names>Emma</given-names></name><xref rid="af015" ref-type="aff">3</xref><xref rid="fn1" ref-type="fn">†</xref></contrib><contrib contrib-type="author"><name><surname>Nitschke</surname><given-names>Katja</given-names></name><xref rid="af005" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Widmeier</surname><given-names>Vanessa</given-names></name><xref rid="af005" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Emmerich</surname><given-names>Florian</given-names></name><xref rid="af020" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Hermle</surname><given-names>Tobias</given-names></name><xref rid="af025" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Gostick</surname><given-names>Emma</given-names></name><xref rid="af030" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Walker</surname><given-names>Andreas</given-names></name><xref rid="af035" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Timm</surname><given-names>Jörg</given-names></name><xref rid="af035" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Price</surname><given-names>David A.</given-names></name><xref rid="af030" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Hofmann</surname><given-names>Maike</given-names></name><xref rid="af005" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Thimme</surname><given-names>Robert</given-names></name><xref rid="af005" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>James</surname><given-names>Edward</given-names></name><xref rid="af015" ref-type="aff">3</xref><xref rid="fn2" ref-type="fn">‡</xref></contrib><contrib contrib-type="author"><name><surname>Neumann-Haefelin</surname><given-names>Christoph</given-names></name><email>christoph.neumann-haefelin@uniklinik-freiburg.de</email><xref rid="af005" ref-type="aff">1</xref><xref rid="cor1" ref-type="corresp">⁎</xref><xref rid="fn2" ref-type="fn">‡</xref></contrib></contrib-group><aff id="af005"><label>1</label>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</aff><aff id="af010"><label>2</label>Faculty of Biology, University of Freiburg, Freiburg, Germany</aff><aff id="af015"><label>3</label>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom</aff><aff id="af020"><label>4</label>Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</aff><aff id="af025"><label>5</label>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany</aff><aff id="af030"><label>6</label>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom</aff><aff id="af035"><label>7</label>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding author. Address: University Hospital Freiburg, Department of Medicine II, Hugstetter Strasse 55, 79106 Freiburg, Germany. Tel.: +49-761-270-32800, fax: +49-761-270-32800. <email>christoph.neumann-haefelin@uniklinik-freiburg.de</email></corresp><fn id="fn1"><label>†</label><p id="np005">Equally contributing first authors.</p></fn><fn id="fn2"><label>‡</label><p id="np010">Equally contributing last authors.</p></fn></author-notes><pub-date pub-type="pmc-release"><day>1</day><month>6</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>6</month><year>2019</year></pub-date><volume>70</volume><issue>6</issue><fpage>1072</fpage><lpage>1081</lpage><history><date date-type="received"><day>25</day><month>6</month><year>2018</year></date><date date-type="rev-recd"><day>30</day><month>1</month><year>2019</year></date><date date-type="accepted"><day>31</day><month>1</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 European Association for the Study of the Liver. Elsevier B.V. All rights reserved.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>European Association for the Study of the Liver</copyright-holder><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</license-p></license></permissions><abstract abstract-type="graphical" id="ab005"><title>Graphical abstract</title><fig id="f0030" position="anchor"><graphic xlink:href="ga1"></graphic></fig></abstract><abstract abstract-type="author-highlights" id="ab010"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0005">ERAP1 polymorphisms are strongly linked with HLA class I-associated autoinflammatory disorders.</p></list-item><list-item id="o0010"><label>•</label><p id="p0010">We identified 2 hypoactive ERAP1 allotypes in an HLA-B*27:05<sup>+</sup> individual with acute HCV infection.</p></list-item><list-item id="o0015"><label>•</label><p id="p0015">These ERAP1 allotypes modified the HCV-specific CD8<sup>+</sup> T cell epitope repertoire <italic>in vivo</italic>, leading to altered immunodominance patterns.</p></list-item><list-item id="o0020"><label>•</label><p id="p0020">Altered immunodominance patterns potentially contributed to the failure of antiviral immunity.</p></list-item></list></p></abstract><abstract id="ab015"><sec><title>Background & Aims</title><p>Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are linked with human leukocyte antigen (HLA) class I-associated autoinflammatory disorders, including ankylosing spondylitis and Behçet’s disease. Disease-associated ERAP1 allotypes exhibit distinct functional properties, but it remains unclear how differential peptide trimming <italic>in vivo</italic> affects the repertoire of epitopes presented to CD8<sup>+</sup> T cells. The aim of this study was to determine the impact of ERAP1 allotypes on the virus-specific CD8<sup>+</sup> T cell epitope repertoire in an HLA-B*27:05<sup>+</sup> individual with acute hepatitis C virus (HCV) infection.</p></sec><sec><title>Methods</title><p>We performed genetic and functional analyses of ERAP1 allotypes and characterized the HCV-specific CD8<sup>+</sup> T cell repertoire at the level of fine epitope specificity and HLA class I restriction, in a patient who had acquired an HCV genotype 1a infection through a needle-stick injury.</p></sec><sec><title>Results</title><p>Two hypoactive allotypic variants of ERAP1 were identified in an individual with acute HCV infection. The associated repertoire of virus-derived epitopes recognized by CD8<sup>+</sup> T cells was uncommon in a couple of respects. Firstly, reactivity was directed away from classically immunodominant epitopes, preferentially targeting either novel or subdominant epitopes. Secondly, reactivity was biased towards longer epitopes (10–11-mers). Despite the patient exhibiting favorable prognostic indicators, these atypical immune responses failed to clear the virus and the patient developed persistent low-level infection with HCV.</p></sec><sec><title>Conclusions</title><p>ERAP1 allotypes modify the virus-specific CD8<sup>+</sup> T cell epitope repertoire <italic>in vivo</italic>, leading to altered immunodominance patterns that may contribute to the failure of antiviral immunity after infection with HCV.</p></sec><sec><title>Lay summary</title><p>Endoplasmic reticulum aminopeptidase 1 (ERAP1) plays a key role in antigen presentation. Genetic variants of <italic>ERAP1</italic> (leading to distinct allotypes) are linked with specific autoinflammatory disorders, such as ankylosing spondylitis and Behçet’s disease. We found that ERAP1 allotypes modified the repertoire of virus-specific CD8<sup>+</sup> T cell epitopes in a patient with hepatitis C virus, leading to an altered pattern of immunodominance that may have contributed to the failure of antiviral immunity in this patient.</p></sec></abstract><kwd-group id="kg005"><title>Keywords</title><kwd>Epitope repertoire</kwd><kwd>ERAP1</kwd><kwd>Hepatitis C virus</kwd><kwd>HLA-B*27</kwd><kwd>T cells</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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