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Healthy human subjects have CD4+ T cells directed against H5N1 influenza virus.

Identifieur interne : 000095 ( 1968/Analysis ); précédent : 000094; suivant : 000096

Healthy human subjects have CD4+ T cells directed against H5N1 influenza virus.

Auteurs : Michelle Roti [États-Unis] ; Junbao Yang ; Deanna Berger ; Laurie Huston ; Eddie A. James ; William W. Kwok

Source :

RBID : pubmed:18209073

Descripteurs français

English descriptors

Abstract

It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus. These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain. However, H5N1 hemagglutinin-reactive CD4(+) T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved. Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes. H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13. These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.

DOI: 10.4049/jimmunol.180.3.1758
PubMed: 18209073


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pubmed:18209073

Le document en format XML

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<name sortKey="Berger, Deanna" sort="Berger, Deanna" uniqKey="Berger D" first="Deanna" last="Berger">Deanna Berger</name>
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<name sortKey="Huston, Laurie" sort="Huston, Laurie" uniqKey="Huston L" first="Laurie" last="Huston">Laurie Huston</name>
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<name sortKey="James, Eddie A" sort="James, Eddie A" uniqKey="James E" first="Eddie A" last="James">Eddie A. James</name>
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<name sortKey="Kwok, William W" sort="Kwok, William W" uniqKey="Kwok W" first="William W" last="Kwok">William W. Kwok</name>
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<title level="j">Journal of immunology (Baltimore, Md. : 1950)</title>
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<term>Amino Acid Sequence</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>Cross Reactions</term>
<term>Epitopes, T-Lymphocyte (chemistry)</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>Female</term>
<term>Hemagglutinins, Viral (chemistry)</term>
<term>Hemagglutinins, Viral (immunology)</term>
<term>Humans</term>
<term>Influenza A Virus, H5N1 Subtype (immunology)</term>
<term>Influenza, Human (immunology)</term>
<term>Male</term>
<term>Molecular Sequence Data</term>
<term>Viral Proteins (chemistry)</term>
<term>Viral Proteins (immunology)</term>
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<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T ()</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Femelle</term>
<term>Grippe humaine (immunologie)</term>
<term>Humains</term>
<term>Hémagglutinines virales ()</term>
<term>Hémagglutinines virales (immunologie)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Mâle</term>
<term>Protéines virales ()</term>
<term>Protéines virales (immunologie)</term>
<term>Réactions croisées</term>
<term>Sous-type H5N1 du virus de la grippe A (immunologie)</term>
<term>Séquence d'acides aminés</term>
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<term>Epitopes, T-Lymphocyte</term>
<term>Hemagglutinins, Viral</term>
<term>Viral Proteins</term>
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<term>Déterminants antigéniques des lymphocytes T</term>
<term>Grippe humaine</term>
<term>Hémagglutinines virales</term>
<term>Lymphocytes T CD4+</term>
<term>Protéines virales</term>
<term>Sous-type H5N1 du virus de la grippe A</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>CD4-Positive T-Lymphocytes</term>
<term>Epitopes, T-Lymphocyte</term>
<term>Hemagglutinins, Viral</term>
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<term>Viral Proteins</term>
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<keywords scheme="MESH" xml:lang="en">
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<term>Cross Reactions</term>
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<term>Hémagglutinines virales</term>
<term>Mâle</term>
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<div type="abstract" xml:lang="en">It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus. These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain. However, H5N1 hemagglutinin-reactive CD4(+) T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved. Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes. H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13. These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.</div>
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