ERAP1 allotypes shape the epitope repertoire of virus-specific CD8+ T cell responses in acute hepatitis C virus infection.
Identifieur interne : 000596 ( PubMed/Checkpoint ); précédent : 000595; suivant : 000597ERAP1 allotypes shape the epitope repertoire of virus-specific CD8+ T cell responses in acute hepatitis C virus infection.
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 [ 1600-0641 ] ; 2019.
Abstract
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 in vivo affects the repertoire of epitopes presented to CD8+ T cells. The aim of this study was to determine the impact of ERAP1 allotypes on the virus-specific CD8+ T cell epitope repertoire in an HLA-B*27:05+ individual with acute hepatitis C virus (HCV) infection.
DOI: 10.1016/j.jhep.2019.01.034
PubMed: 30769005
Affiliations:
- Allemagne, Royaume-Uni
- Bade-Wurtemberg, District de Düsseldorf, District de Fribourg-en-Brisgau, Rhénanie-du-Nord-Westphalie
- Düsseldorf, Fribourg-en-Brisgau
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type="city">Fribourg-en-Brisgau</settlement></placeName></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:affiliation>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom.</nlm:affiliation><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><wicri:noRegion>Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Nitschke, Katja" sort="Nitschke, Katja" uniqKey="Nitschke K" first="Katja" last="Nitschke">Katja Nitschke</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Widmeier, Vanessa" sort="Widmeier, Vanessa" uniqKey="Widmeier V" first="Vanessa" last="Widmeier">Vanessa Widmeier</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region 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type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Hermle, Tobias" sort="Hermle, Tobias" uniqKey="Hermle T" first="Tobias" last="Hermle">Tobias Hermle</name><affiliation wicri:level="3"><nlm:affiliation>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></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:affiliation>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea><wicri:noRegion>Cardiff</wicri:noRegion></affiliation></author><author><name sortKey="Walker, Andreas" sort="Walker, Andreas" uniqKey="Walker A" first="Andreas" last="Walker">Andreas Walker</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Düsseldorf</region><settlement type="city">Düsseldorf</settlement></placeName></affiliation></author><author><name sortKey="Timm, Jorg" sort="Timm, Jorg" uniqKey="Timm J" first="Jörg" last="Timm">Jörg Timm</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Düsseldorf</region><settlement type="city">Düsseldorf</settlement></placeName></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:affiliation>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea><wicri:noRegion>Cardiff</wicri:noRegion></affiliation></author><author><name sortKey="Hofmann, Maike" sort="Hofmann, Maike" uniqKey="Hofmann M" first="Maike" last="Hofmann">Maike Hofmann</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Thimme, Robert" sort="Thimme, Robert" uniqKey="Thimme R" first="Robert" last="Thimme">Robert Thimme</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></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:affiliation>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom.</nlm:affiliation><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><wicri:noRegion>Southampton</wicri:noRegion></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="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: christoph.neumann-haefelin@uniklinik-freiburg.de.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30769005</idno><idno type="pmid">30769005</idno><idno type="doi">10.1016/j.jhep.2019.01.034</idno><idno type="wicri:Area/PubMed/Corpus">000644</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000644</idno><idno type="wicri:Area/PubMed/Curation">000644</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000644</idno><idno type="wicri:Area/PubMed/Checkpoint">000596</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000596</idno></publicationStmt><sourceDesc><biblStruct><analytic><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="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></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:affiliation>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom.</nlm:affiliation><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><wicri:noRegion>Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Nitschke, Katja" sort="Nitschke, Katja" uniqKey="Nitschke K" first="Katja" last="Nitschke">Katja Nitschke</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Widmeier, Vanessa" sort="Widmeier, Vanessa" uniqKey="Widmeier V" first="Vanessa" last="Widmeier">Vanessa Widmeier</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Emmerich, Florian" sort="Emmerich, Florian" uniqKey="Emmerich F" first="Florian" last="Emmerich">Florian Emmerich</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Hermle, Tobias" sort="Hermle, Tobias" uniqKey="Hermle T" first="Tobias" last="Hermle">Tobias Hermle</name><affiliation wicri:level="3"><nlm:affiliation>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></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:affiliation>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea><wicri:noRegion>Cardiff</wicri:noRegion></affiliation></author><author><name sortKey="Walker, Andreas" sort="Walker, Andreas" uniqKey="Walker A" first="Andreas" last="Walker">Andreas Walker</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Düsseldorf</region><settlement type="city">Düsseldorf</settlement></placeName></affiliation></author><author><name sortKey="Timm, Jorg" sort="Timm, Jorg" uniqKey="Timm J" first="Jörg" last="Timm">Jörg Timm</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, Heinrich Heine University, Düsseldorf</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Düsseldorf</region><settlement type="city">Düsseldorf</settlement></placeName></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:affiliation>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff</wicri:regionArea><wicri:noRegion>Cardiff</wicri:noRegion></affiliation></author><author><name sortKey="Hofmann, Maike" sort="Hofmann, Maike" uniqKey="Hofmann M" first="Maike" last="Hofmann">Maike Hofmann</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Thimme, Robert" sort="Thimme, Robert" uniqKey="Thimme R" first="Robert" last="Thimme">Robert Thimme</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></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:affiliation>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom.</nlm:affiliation><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><wicri:noRegion>Southampton</wicri:noRegion></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="3"><nlm:affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: christoph.neumann-haefelin@uniklinik-freiburg.de.</nlm:affiliation><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><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author></analytic><series><title level="j">Journal of hepatology</title><idno type="eISSN">1600-0641</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 in vivo 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.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">30769005</PMID><DateRevised><Year>2020</Year><Month>02</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1600-0641</ISSN><JournalIssue CitedMedium="Internet"><Volume>70</Volume><Issue>6</Issue><PubDate><Year>2019</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Journal of hepatology</Title><ISOAbbreviation>J. Hepatol.</ISOAbbreviation></Journal><ArticleTitle>ERAP1 allotypes shape the epitope repertoire of virus-specific CD8<sup>+</sup> T cell responses in acute hepatitis C virus infection.</ArticleTitle><Pagination><MedlinePgn>1072-1081</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0168-8278(19)30111-4</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jhep.2019.01.034</ELocationID><Abstract><AbstractText Label="BACKGROUND & AIMS" NlmCategory="OBJECTIVE">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 in vivo 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.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">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.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">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.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">ERAP1 allotypes modify the virus-specific CD8<sup>+</sup> T cell epitope repertoire in vivo, leading to altered immunodominance patterns that may contribute to the failure of antiviral immunity after infection with HCV.</AbstractText><AbstractText Label="LAY SUMMARY" NlmCategory="UNASSIGNED">Endoplasmic reticulum aminopeptidase 1 (ERAP1) plays a key role in antigen presentation. Genetic variants of ERAP1 (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.</AbstractText><CopyrightInformation>Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kemming</LastName><ForeName>Janine</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reeves</LastName><ForeName>Emma</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nitschke</LastName><ForeName>Katja</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Widmeier</LastName><ForeName>Vanessa</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Emmerich</LastName><ForeName>Florian</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institute of Transfusion Medicine and Gene Therapy, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hermle</LastName><ForeName>Tobias</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Renal Division, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gostick</LastName><ForeName>Emma</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Walker</LastName><ForeName>Andreas</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Timm</LastName><ForeName>Jörg</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute for Virology, Heinrich Heine University, Düsseldorf, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Price</LastName><ForeName>David A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hofmann</LastName><ForeName>Maike</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thimme</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>James</LastName><ForeName>Edward</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neumann-Haefelin</LastName><ForeName>Christoph</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Medicine II, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: christoph.neumann-haefelin@uniklinik-freiburg.de.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>02</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Hepatol</MedlineTA><NlmUniqueID>8503886</NlmUniqueID><ISSNLinking>0168-8278</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">ERAP1</Keyword><Keyword MajorTopicYN="N">Epitope repertoire</Keyword><Keyword MajorTopicYN="N">HLA-B*27</Keyword><Keyword MajorTopicYN="N">Hepatitis C virus</Keyword><Keyword MajorTopicYN="N">T cells</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>06</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>01</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>01</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30769005</ArticleId><ArticleId IdType="pii">S0168-8278(19)30111-4</ArticleId><ArticleId IdType="doi">10.1016/j.jhep.2019.01.034</ArticleId><ArticleId IdType="pmc">PMC6527866</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>J Exp Med. 2001 Nov 19;194(10):1395-406</Citation><ArticleIdList><ArticleId 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