Multiple HLA A11-restricted cytotoxic T-lymphocyte epitopes of different immunogenicities in the Epstein-Barr virus-encoded nuclear antigen 4.
Identifieur interne : 004516 ( Main/Exploration ); précédent : 004515; suivant : 004517Multiple HLA A11-restricted cytotoxic T-lymphocyte epitopes of different immunogenicities in the Epstein-Barr virus-encoded nuclear antigen 4.
Auteurs : R. Gavioli [Suède] ; M G Kurilla ; P O De Campos-Lima ; L E Wallace ; R. Dolcetti ; R J Murray ; A B Rickinson ; M G MasucciSource :
- Journal of virology [ 0022-538X ] ; 1993.
Descripteurs français
- KwdFr :
- Analyse de mutations d'ADN, Antigène HLA-A11, Antigènes HLA-A (immunologie), Antigènes nucléaires du virus d'Epstein-Barr, Antigènes viraux (immunologie), Cellules cultivées, Données de séquences moléculaires, Fragments peptidiques (immunologie), Fragments peptidiques (synthèse chimique), Herpèsvirus humain de type 4 (immunologie), Humains, Lymphocytes T cytotoxiques (immunologie), Noyau de la cellule (immunologie), Production d'anticorps, Protéines de liaison à l'ADN (immunologie), Spécificité des anticorps, Séquence d'acides aminés, Séquence nucléotidique, Vecteurs génétiques, Virus de la vaccine (génétique), Épitopes (immunologie).
- MESH :
- génétique : Virus de la vaccine.
- immunologie : Antigènes HLA-A, Antigènes viraux, Fragments peptidiques, Herpèsvirus humain de type 4, Lymphocytes T cytotoxiques, Noyau de la cellule, Protéines de liaison à l'ADN, Épitopes.
- synthèse chimique : Fragments peptidiques.
- Analyse de mutations d'ADN, Antigène HLA-A11, Antigènes nucléaires du virus d'Epstein-Barr, Cellules cultivées, Données de séquences moléculaires, Humains, Production d'anticorps, Spécificité des anticorps, Séquence d'acides aminés, Séquence nucléotidique, Vecteurs génétiques.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antibody Formation, Antibody Specificity, Antigens, Viral (immunology), Base Sequence, Cell Nucleus (immunology), Cells, Cultured, DNA Mutational Analysis, DNA-Binding Proteins (immunology), Epitopes (immunology), Epstein-Barr Virus Nuclear Antigens, Genetic Vectors, HLA-A Antigens (immunology), HLA-A11 Antigen, Herpesvirus 4, Human (immunology), Humans, Molecular Sequence Data, Peptide Fragments (chemical synthesis), Peptide Fragments (immunology), T-Lymphocytes, Cytotoxic (immunology), Vaccinia virus (genetics).
- MESH :
- chemical , chemical synthesis : Peptide Fragments.
- chemical , immunology : Antigens, Viral, DNA-Binding Proteins, Epitopes, HLA-A Antigens, Peptide Fragments.
- genetics : Vaccinia virus.
- immunology : Cell Nucleus, Herpesvirus 4, Human, T-Lymphocytes, Cytotoxic.
- Amino Acid Sequence, Antibody Formation, Antibody Specificity, Base Sequence, Cells, Cultured, DNA Mutational Analysis, Epstein-Barr Virus Nuclear Antigens, Genetic Vectors, HLA-A11 Antigen, Humans, Molecular Sequence Data.
Abstract
Epstein-Barr virus (EBV), a ubiquitous herpesvirus, induces potent HLA class I-restricted cytotoxic T-lymphocyte (CTL) responses. Analyses of target antigen choice have shown that the very strong CTL responses which are often observed through the HLA A11 allele map are due almost entirely to a single transformation-associated EBV protein, the nuclear antigen EBNA4. Here, we sought to determine the number and relative immunogenicities of HLA A11-restricted epitopes within this 938-amino-acid protein. An initial screening with a series of recombinant vaccinia virus vectors encoding progressively truncated forms of EBNA4 was followed by peptide sensitization experiments using overlapping 14- or 15-mers from the entire sequence. These two approaches allowed the identification of five epitope regions located between residues 101 and 115, 416 and 429, 396 and 410, 481 and 495, and 551 and 564 of the EBNA4 molecule. CTL preparations from all seven HLA A11-positive donors tested had demonstrable reactivities against the 416-to-429 peptide, whereas reactivities against the other epitopes either tended to be lost on serial passage or, for some of the donors, were never detected. The immunodominance of the 416-to-429 epitope was further supported by peptide dilution assays using polyclonal effectors and by CTL cloning experiments. Analysis of the 416-to-429 region identified the nanomer 416-424 (IVTDFSVIK) as the cognate peptide. This peptide was able to sensitize targets to lysis by A11-restricted CTL clones at concentrations as low as 5 x 10(-14) M.
PubMed: 7679748
Affiliations:
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Gavioli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Tumor Biology, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Kurilla, M G" sort="Kurilla, M G" uniqKey="Kurilla M" first="M G" last="Kurilla">M G Kurilla</name></author><author><name sortKey="De Campos Lima, P O" sort="De Campos Lima, P O" uniqKey="De Campos Lima P" first="P O" last="De Campos-Lima">P O De Campos-Lima</name></author><author><name sortKey="Wallace, L E" sort="Wallace, L E" uniqKey="Wallace L" first="L E" last="Wallace">L E Wallace</name></author><author><name sortKey="Dolcetti, R" sort="Dolcetti, R" uniqKey="Dolcetti R" first="R" last="Dolcetti">R. 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Gavioli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Tumor Biology, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Kurilla, M G" sort="Kurilla, M G" uniqKey="Kurilla M" first="M G" last="Kurilla">M G Kurilla</name></author><author><name sortKey="De Campos Lima, P O" sort="De Campos Lima, P O" uniqKey="De Campos Lima P" first="P O" last="De Campos-Lima">P O De Campos-Lima</name></author><author><name sortKey="Wallace, L E" sort="Wallace, L E" uniqKey="Wallace L" first="L E" last="Wallace">L E Wallace</name></author><author><name sortKey="Dolcetti, R" sort="Dolcetti, R" uniqKey="Dolcetti R" first="R" last="Dolcetti">R. Dolcetti</name></author><author><name sortKey="Murray, R J" sort="Murray, R J" uniqKey="Murray R" first="R J" last="Murray">R J Murray</name></author><author><name sortKey="Rickinson, A B" sort="Rickinson, A B" uniqKey="Rickinson A" first="A B" last="Rickinson">A B Rickinson</name></author><author><name sortKey="Masucci, M G" sort="Masucci, M G" uniqKey="Masucci M" first="M G" last="Masucci">M G Masucci</name></author></analytic><series><title level="j">Journal of virology</title><idno type="ISSN">0022-538X</idno><imprint><date when="1993" type="published">1993</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antibody Formation</term><term>Antibody Specificity</term><term>Antigens, Viral (immunology)</term><term>Base Sequence</term><term>Cell Nucleus (immunology)</term><term>Cells, Cultured</term><term>DNA Mutational Analysis</term><term>DNA-Binding Proteins (immunology)</term><term>Epitopes (immunology)</term><term>Epstein-Barr Virus Nuclear Antigens</term><term>Genetic Vectors</term><term>HLA-A Antigens (immunology)</term><term>HLA-A11 Antigen</term><term>Herpesvirus 4, Human (immunology)</term><term>Humans</term><term>Molecular Sequence Data</term><term>Peptide Fragments (chemical synthesis)</term><term>Peptide Fragments (immunology)</term><term>T-Lymphocytes, Cytotoxic (immunology)</term><term>Vaccinia virus (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Antigène HLA-A11</term><term>Antigènes HLA-A (immunologie)</term><term>Antigènes nucléaires du virus d'Epstein-Barr</term><term>Antigènes viraux (immunologie)</term><term>Cellules cultivées</term><term>Données de séquences moléculaires</term><term>Fragments peptidiques (immunologie)</term><term>Fragments peptidiques (synthèse chimique)</term><term>Herpèsvirus humain de type 4 (immunologie)</term><term>Humains</term><term>Lymphocytes T cytotoxiques (immunologie)</term><term>Noyau de la cellule (immunologie)</term><term>Production d'anticorps</term><term>Protéines de liaison à l'ADN (immunologie)</term><term>Spécificité des anticorps</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Vecteurs génétiques</term><term>Virus de la vaccine (génétique)</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Peptide Fragments</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term><term>DNA-Binding Proteins</term><term>Epitopes</term><term>HLA-A Antigens</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Vaccinia virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Virus de la vaccine</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes HLA-A</term><term>Antigènes viraux</term><term>Fragments peptidiques</term><term>Herpèsvirus humain de type 4</term><term>Lymphocytes T cytotoxiques</term><term>Noyau de la cellule</term><term>Protéines de liaison à l'ADN</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cell Nucleus</term><term>Herpesvirus 4, Human</term><term>T-Lymphocytes, Cytotoxic</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Fragments peptidiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Antibody Formation</term><term>Antibody Specificity</term><term>Base Sequence</term><term>Cells, Cultured</term><term>DNA Mutational Analysis</term><term>Epstein-Barr Virus Nuclear Antigens</term><term>Genetic Vectors</term><term>HLA-A11 Antigen</term><term>Humans</term><term>Molecular Sequence Data</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Antigène HLA-A11</term><term>Antigènes nucléaires du virus d'Epstein-Barr</term><term>Cellules cultivées</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Production d'anticorps</term><term>Spécificité des anticorps</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Vecteurs génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Epstein-Barr virus (EBV), a ubiquitous herpesvirus, induces potent HLA class I-restricted cytotoxic T-lymphocyte (CTL) responses. Analyses of target antigen choice have shown that the very strong CTL responses which are often observed through the HLA A11 allele map are due almost entirely to a single transformation-associated EBV protein, the nuclear antigen EBNA4. Here, we sought to determine the number and relative immunogenicities of HLA A11-restricted epitopes within this 938-amino-acid protein. An initial screening with a series of recombinant vaccinia virus vectors encoding progressively truncated forms of EBNA4 was followed by peptide sensitization experiments using overlapping 14- or 15-mers from the entire sequence. These two approaches allowed the identification of five epitope regions located between residues 101 and 115, 416 and 429, 396 and 410, 481 and 495, and 551 and 564 of the EBNA4 molecule. CTL preparations from all seven HLA A11-positive donors tested had demonstrable reactivities against the 416-to-429 peptide, whereas reactivities against the other epitopes either tended to be lost on serial passage or, for some of the donors, were never detected. The immunodominance of the 416-to-429 epitope was further supported by peptide dilution assays using polyclonal effectors and by CTL cloning experiments. Analysis of the 416-to-429 region identified the nanomer 416-424 (IVTDFSVIK) as the cognate peptide. This peptide was able to sensitize targets to lysis by A11-restricted CTL clones at concentrations as low as 5 x 10(-14) M.</div></front></TEI><affiliations><list><country><li>Suède</li></country><region><li>Svealand</li></region><settlement><li>Stockholm</li></settlement></list><tree><noCountry><name sortKey="De Campos Lima, P O" sort="De Campos Lima, P O" uniqKey="De Campos Lima P" first="P O" last="De Campos-Lima">P O De Campos-Lima</name><name sortKey="Dolcetti, R" sort="Dolcetti, R" uniqKey="Dolcetti R" first="R" last="Dolcetti">R. Dolcetti</name><name sortKey="Kurilla, M G" sort="Kurilla, M G" uniqKey="Kurilla M" first="M G" last="Kurilla">M G Kurilla</name><name sortKey="Masucci, M G" sort="Masucci, M G" uniqKey="Masucci M" first="M G" last="Masucci">M G Masucci</name><name sortKey="Murray, R J" sort="Murray, R J" uniqKey="Murray R" first="R J" last="Murray">R J Murray</name><name sortKey="Rickinson, A B" sort="Rickinson, A B" uniqKey="Rickinson A" first="A B" last="Rickinson">A B Rickinson</name><name sortKey="Wallace, L E" sort="Wallace, L E" uniqKey="Wallace L" first="L E" last="Wallace">L E Wallace</name></noCountry><country name="Suède"><region name="Svealand"><name sortKey="Gavioli, R" sort="Gavioli, R" uniqKey="Gavioli R" first="R" last="Gavioli">R. Gavioli</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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