Minimal T-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4+ T-cell epitopes within hepatitis C virus NS3 and NS4 proteins!
Identifieur interne : 003029 ( Main/Exploration ); précédent : 003028; suivant : 003030Minimal T-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4+ T-cell epitopes within hepatitis C virus NS3 and NS4 proteins!
Auteurs : J. T. Gerlach [Suisse, Allemagne] ; A. Ulsenheimer [Allemagne] ; N. H. Grüner [Allemagne] ; M.-C. June [Allemagne] ; W. Schraut [Allemagne] ; C.-A. Schirren [Allemagne] ; M. Heeg [Allemagne] ; S. Scholz [Allemagne] ; K. Witter [Allemagne] ; R. Zahn [Allemagne] ; A. Vogler [Allemagne] ; R. Zachoval [Allemagne] ; G. R. Pape [Allemagne] ; H. M. Diepolder [Allemagne]Source :
- Journal of virology [ 0022-538X ] ; 2005.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Adolescent, Adulte, Adulte d'âge moyen, Agranulocytes (immunologie), Allèles, Antigènes HLA (génétique), Antigènes HLA (physiologie), Données de séquences moléculaires, Femelle, Hepacivirus (immunologie), Humains, Hépatite C (immunologie), Lymphocytes T CD4+ (immunologie), Mâle, Protéines virales non structurales (immunologie), Présentation d'antigène, Séquence d'acides aminés, Épitopes immunodominants.
- MESH :
- génétique : Antigènes HLA.
- immunologie : Agranulocytes, Hepacivirus, Hépatite C, Lymphocytes T CD4+, Protéines virales non structurales.
- physiologie : Antigènes HLA.
- Pascal (Inist)
- Activation des lymphocytes, Adolescent, Adulte, Adulte d'âge moyen, Allèles, Données de séquences moléculaires, Femelle, Humains, Mâle, Présentation d'antigène, Séquence d'acides aminés, Virus hépatite C, Lymphocyte T, Système HLA, Immunodominance, Déterminant antigénique, Protéine, Microbiologie, Virologie, Antigène CD4, Épitopes immunodominants.
English descriptors
- KwdEn :
- Adolescent, Adult, Alleles, Amino Acid Sequence, Antigen Presentation, Antigenic determinant, CD4-Positive T-Lymphocytes (immunology), Female, HLA Antigens (genetics), HLA Antigens (physiology), HLA-System, Hepacivirus (immunology), Hepatitis C (immunology), Hepatitis C virus, Humans, Immunodominance, Immunodominant Epitopes, Leukocytes, Mononuclear (immunology), Lymphocyte Activation, Male, Microbiology, Middle Aged, Molecular Sequence Data, Protein, T-Lymphocyte, Viral Nonstructural Proteins (immunology), Virology.
- MESH :
- chemical , genetics : HLA Antigens.
- immunology : CD4-Positive T-Lymphocytes, Hepacivirus, Hepatitis C, Leukocytes, Mononuclear, Viral Nonstructural Proteins.
- chemical , physiology : HLA Antigens.
- Adolescent, Adult, Alleles, Amino Acid Sequence, Antigen Presentation, Female, Humans, Immunodominant Epitopes, Lymphocyte Activation, Male, Middle Aged, Molecular Sequence Data.
Abstract
The hepatitis C virus (HCV)-specific CD4+ T-cell response against nonstructural proteins is strongly associated with successful viral clearance during acute hepatitis C. To further develop these observations into peptide-based vaccines and clinical immunomonitoring tools like HLA class II tetramers, a detailed characterization of immunodominant CD4+ T-cell epitopes is required. We studied peripheral blood mononuclear cells from 20 patients with acute hepatitis C using 83 overlapping 20-mer peptides covering the NS3 helicase and NS4. Eight peptides were recognized by ≥40% of patients, and specific CD4+ T-cell clones were obtained for seven of these and three additional, subdominant epitopes. Mapping of minimal stimulatory sequences defined epitopes of 8 to 13 amino acids in length, but optimal T-cell stimulation was observed with 10- to 15-mers. While some epitopes were presented by different HLA molecules, others were presented by only a single HLA class II molecule, which has implications for patient selection in clinical trials of peptide-based immunotherapies. In conclusion, using two different approaches we identified and characterized a set of CD4+ T-cell epitopes in the HCV NS3-NS4 region which are immunodominant in patients achieving transient or persistent viral control. This information allows the construction of a valuable panel of HCV-specific HLA class II tetramers for further study of CD4+ T-cell responses in chronic hepatitis C. The finding of immunodominant epitopes with very constrained HLA restriction has implications for patient selection in clinical trials of peptide-based immunotherapies.
Affiliations:
- Allemagne, Suisse
- Bavière, District de Haute-Bavière
- Munich
- Université Louis-et-Maximilien de Munich
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Le document en format XML
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Scholz</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Witter, K" sort="Witter, K" uniqKey="Witter K" first="K." last="Witter">K. Witter</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Zahn, R" sort="Zahn, R" uniqKey="Zahn R" first="R." last="Zahn">R. Zahn</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Vogler, A" sort="Vogler, A" uniqKey="Vogler A" first="A." last="Vogler">A. Vogler</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Zachoval, R" sort="Zachoval, R" uniqKey="Zachoval R" first="R." last="Zachoval">R. Zachoval</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Pape, G R" sort="Pape, G R" uniqKey="Pape G" first="G. R." last="Pape">G. R. Pape</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Diepolder, H M" sort="Diepolder, H M" uniqKey="Diepolder H" first="H. M." last="Diepolder">H. M. Diepolder</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">05-0432453</idno><date when="2005">2005</date><idno type="stanalyst">PASCAL 05-0432453 INIST</idno><idno type="RBID">Pascal:05-0432453</idno><idno type="wicri:Area/PascalFrancis/Corpus">000078</idno><idno type="wicri:Area/PascalFrancis/Curation">000016</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000079</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000079</idno><idno type="wicri:doubleKey">0022-538X:2005:Gerlach J:minimal:t:cell</idno><idno type="wicri:Area/Main/Merge">003060</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:16160170</idno><idno type="wicri:Area/PubMed/Corpus">002311</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002311</idno><idno type="wicri:Area/PubMed/Curation">002311</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002311</idno><idno type="wicri:Area/PubMed/Checkpoint">002193</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002193</idno><idno type="wicri:Area/Ncbi/Merge">000369</idno><idno type="wicri:Area/Ncbi/Curation">000369</idno><idno type="wicri:Area/Ncbi/Checkpoint">000369</idno><idno type="wicri:doubleKey">0022-538X:2005:Gerlach J:minimal:t:cell</idno><idno type="wicri:Area/Main/Merge">002F24</idno><idno type="wicri:Area/Main/Curation">003029</idno><idno type="wicri:Area/Main/Exploration">003029</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Minimal T-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4<sup>+</sup> T-cell epitopes within hepatitis C virus NS3 and NS4 proteins!</title><author><name sortKey="Gerlach, J T" sort="Gerlach, J T" uniqKey="Gerlach J" first="J. T." last="Gerlach">J. T. Gerlach</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Gastroenterology and Hepatology, University Hospital Zurich</s1><s2>8091 Zurich</s2><s3>CHE</s3><sZ>1 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>8091 Zurich</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Ulsenheimer, A" sort="Ulsenheimer, A" uniqKey="Ulsenheimer A" first="A." last="Ulsenheimer">A. Ulsenheimer</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Gruner, N H" sort="Gruner, N H" uniqKey="Gruner N" first="N. H." last="Grüner">N. H. Grüner</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="June, M C" sort="June, M C" uniqKey="June M" first="M.-C." last="June">M.-C. June</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Schraut, W" sort="Schraut, W" uniqKey="Schraut W" first="W." last="Schraut">W. Schraut</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Schirren, C A" sort="Schirren, C A" uniqKey="Schirren C" first="C.-A." last="Schirren">C.-A. Schirren</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Heeg, M" sort="Heeg, M" uniqKey="Heeg M" first="M." last="Heeg">M. Heeg</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Scholz, S" sort="Scholz, S" uniqKey="Scholz S" first="S." last="Scholz">S. Scholz</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Witter, K" sort="Witter, K" uniqKey="Witter K" first="K." last="Witter">K. Witter</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Zahn, R" sort="Zahn, R" uniqKey="Zahn R" first="R." last="Zahn">R. Zahn</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Vogler, A" sort="Vogler, A" uniqKey="Vogler A" first="A." last="Vogler">A. Vogler</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Immunogenetics Laboratory, Kinderpoliklinik, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Zachoval, R" sort="Zachoval, R" uniqKey="Zachoval R" first="R." last="Zachoval">R. Zachoval</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Pape, G R" sort="Pape, G R" uniqKey="Pape G" first="G. R." last="Pape">G. R. Pape</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author><author><name sortKey="Diepolder, H M" sort="Diepolder, H M" uniqKey="Diepolder H" first="H. M." last="Diepolder">H. M. Diepolder</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Institute for Immunology, University of Munich</s1><s2>80336 Munich</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Medicine II, Klinikum Grosshadem, University of Munich</s1><s2>81377 Munich</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université Louis-et-Maximilien de Munich</orgName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Alleles</term><term>Amino Acid Sequence</term><term>Antigen Presentation</term><term>Antigenic determinant</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>Female</term><term>HLA Antigens (genetics)</term><term>HLA Antigens (physiology)</term><term>HLA-System</term><term>Hepacivirus (immunology)</term><term>Hepatitis C (immunology)</term><term>Hepatitis C virus</term><term>Humans</term><term>Immunodominance</term><term>Immunodominant Epitopes</term><term>Leukocytes, Mononuclear (immunology)</term><term>Lymphocyte Activation</term><term>Male</term><term>Microbiology</term><term>Middle Aged</term><term>Molecular Sequence Data</term><term>Protein</term><term>T-Lymphocyte</term><term>Viral Nonstructural Proteins (immunology)</term><term>Virology</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Agranulocytes (immunologie)</term><term>Allèles</term><term>Antigènes HLA (génétique)</term><term>Antigènes HLA (physiologie)</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Hepacivirus (immunologie)</term><term>Humains</term><term>Hépatite C (immunologie)</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Mâle</term><term>Protéines virales non structurales (immunologie)</term><term>Présentation d'antigène</term><term>Séquence d'acides aminés</term><term>Épitopes immunodominants</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>HLA Antigens</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes HLA</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Agranulocytes</term><term>Hepacivirus</term><term>Hépatite C</term><term>Lymphocytes T CD4+</term><term>Protéines virales non structurales</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>Hepacivirus</term><term>Hepatitis C</term><term>Leukocytes, Mononuclear</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Antigènes HLA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>HLA Antigens</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Alleles</term><term>Amino Acid Sequence</term><term>Antigen Presentation</term><term>Female</term><term>Humans</term><term>Immunodominant Epitopes</term><term>Lymphocyte Activation</term><term>Male</term><term>Middle Aged</term><term>Molecular Sequence Data</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Activation des lymphocytes</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Allèles</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Présentation d'antigène</term><term>Séquence d'acides aminés</term><term>Virus hépatite C</term><term>Lymphocyte T</term><term>Système HLA</term><term>Immunodominance</term><term>Déterminant antigénique</term><term>Protéine</term><term>Microbiologie</term><term>Virologie</term><term>Antigène CD4</term><term>Épitopes immunodominants</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The hepatitis C virus (HCV)-specific CD4<sup>+</sup> T-cell response against nonstructural proteins is strongly associated with successful viral clearance during acute hepatitis C. To further develop these observations into peptide-based vaccines and clinical immunomonitoring tools like HLA class II tetramers, a detailed characterization of immunodominant CD4<sup>+</sup> T-cell epitopes is required. We studied peripheral blood mononuclear cells from 20 patients with acute hepatitis C using 83 overlapping 20-mer peptides covering the NS3 helicase and NS4. Eight peptides were recognized by ≥40% of patients, and specific CD4<sup>+</sup> T-cell clones were obtained for seven of these and three additional, subdominant epitopes. Mapping of minimal stimulatory sequences defined epitopes of 8 to 13 amino acids in length, but optimal T-cell stimulation was observed with 10- to 15-mers. While some epitopes were presented by different HLA molecules, others were presented by only a single HLA class II molecule, which has implications for patient selection in clinical trials of peptide-based immunotherapies. In conclusion, using two different approaches we identified and characterized a set of CD4<sup>+</sup> T-cell epitopes in the HCV NS3-NS4 region which are immunodominant in patients achieving transient or persistent viral control. This information allows the construction of a valuable panel of HCV-specific HLA class II tetramers for further study of CD4<sup>+</sup> T-cell responses in chronic hepatitis C. The finding of immunodominant epitopes with very constrained HLA restriction has implications for patient selection in clinical trials of peptide-based immunotherapies.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Suisse</li></country><region><li>Bavière</li><li>District de Haute-Bavière</li></region><settlement><li>Munich</li></settlement><orgName><li>Université Louis-et-Maximilien de Munich</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Gerlach, J T" sort="Gerlach, J T" uniqKey="Gerlach J" first="J. T." last="Gerlach">J. T. Gerlach</name></noRegion></country><country name="Allemagne"><region name="Bavière"><name sortKey="Gerlach, J T" sort="Gerlach, J T" uniqKey="Gerlach J" first="J. T." last="Gerlach">J. T. Gerlach</name></region><name sortKey="Diepolder, H M" sort="Diepolder, H M" uniqKey="Diepolder H" first="H. M." last="Diepolder">H. M. Diepolder</name><name sortKey="Diepolder, H M" sort="Diepolder, H M" uniqKey="Diepolder H" first="H. M." last="Diepolder">H. M. Diepolder</name><name sortKey="Gruner, N H" sort="Gruner, N H" uniqKey="Gruner N" first="N. H." last="Grüner">N. H. Grüner</name><name sortKey="Gruner, N H" sort="Gruner, N H" uniqKey="Gruner N" first="N. H." last="Grüner">N. H. Grüner</name><name sortKey="Heeg, M" sort="Heeg, M" uniqKey="Heeg M" first="M." last="Heeg">M. Heeg</name><name sortKey="June, M C" sort="June, M C" uniqKey="June M" first="M.-C." last="June">M.-C. June</name><name sortKey="June, M C" sort="June, M C" uniqKey="June M" first="M.-C." last="June">M.-C. June</name><name sortKey="Pape, G R" sort="Pape, G R" uniqKey="Pape G" first="G. R." last="Pape">G. R. Pape</name><name sortKey="Pape, G R" sort="Pape, G R" uniqKey="Pape G" first="G. R." last="Pape">G. R. Pape</name><name sortKey="Schirren, C A" sort="Schirren, C A" uniqKey="Schirren C" first="C.-A." last="Schirren">C.-A. Schirren</name><name sortKey="Scholz, S" sort="Scholz, S" uniqKey="Scholz S" first="S." last="Scholz">S. Scholz</name><name sortKey="Schraut, W" sort="Schraut, W" uniqKey="Schraut W" first="W." last="Schraut">W. Schraut</name><name sortKey="Ulsenheimer, A" sort="Ulsenheimer, A" uniqKey="Ulsenheimer A" first="A." last="Ulsenheimer">A. Ulsenheimer</name><name sortKey="Ulsenheimer, A" sort="Ulsenheimer, A" uniqKey="Ulsenheimer A" first="A." last="Ulsenheimer">A. Ulsenheimer</name><name sortKey="Vogler, A" sort="Vogler, A" uniqKey="Vogler A" first="A." last="Vogler">A. Vogler</name><name sortKey="Witter, K" sort="Witter, K" uniqKey="Witter K" first="K." last="Witter">K. Witter</name><name sortKey="Zachoval, R" sort="Zachoval, R" uniqKey="Zachoval R" first="R." last="Zachoval">R. Zachoval</name><name sortKey="Zahn, R" sort="Zahn, R" uniqKey="Zahn R" first="R." last="Zahn">R. Zahn</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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