SARS coronavirus nucleocapsid immunodominant T-cell epitope cluster is common to both exogenous recombinant and endogenous DNA-encoded immunogens.
Identifieur interne : 003D33 ( Main/Exploration ); précédent : 003D32; suivant : 003D34SARS coronavirus nucleocapsid immunodominant T-cell epitope cluster is common to both exogenous recombinant and endogenous DNA-encoded immunogens.
Auteurs : Vandana Gupta [Singapour] ; Tani M. Tabiin ; Kai Sun ; Ananth Chandrasekaran ; Azlinda Anwar ; Kun Yang ; Priya Chikhlikar ; Jerome Salmon ; Vladimir Brusic ; Ernesto T A. Marques ; Srinivasan N. Kellathur ; Thomas J. AugustSource :
- Virology [ 0042-6822 ] ; 2006.
Descripteurs français
- KwdFr :
- ADN viral (génétique), Animaux, Antigènes viraux (génétique), Cellules COS, Données de séquences moléculaires, Lignée cellulaire, Lymphocytes T (immunologie), Microscopie immunoélectronique, Protéines de fusion recombinantes (génétique), Protéines de fusion recombinantes (immunologie), Protéines nucléocapside (génétique), Protéines nucléocapside (immunologie), Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Présentation d'antigène, Souris, Spodoptera, Séquence d'acides aminés, Séquence nucléotidique, Transfection, Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Virus du SRAS (génétique), Virus du SRAS (immunologie), Épitopes immunodominants (génétique).
- MESH :
- génétique : ADN viral, Antigènes viraux, Protéines de fusion recombinantes, Protéines nucléocapside, Protéines recombinantes, Vaccins antiviraux, Virus du SRAS, Épitopes immunodominants.
- immunologie : Lymphocytes T, Protéines de fusion recombinantes, Protéines nucléocapside, Protéines recombinantes, Vaccins antiviraux, Virus du SRAS.
- Animaux, Cellules COS, Données de séquences moléculaires, Lignée cellulaire, Microscopie immunoélectronique, Présentation d'antigène, Souris, Spodoptera, Séquence d'acides aminés, Séquence nucléotidique, Transfection.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antigen Presentation, Antigens, Viral (genetics), Base Sequence, COS Cells, Cell Line, Chlorocebus aethiops, DNA, Viral (genetics), Immunodominant Epitopes (genetics), Mice, Microscopy, Immunoelectron, Molecular Sequence Data, Nucleocapsid Proteins (genetics), Nucleocapsid Proteins (immunology), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (immunology), Recombinant Proteins (genetics), Recombinant Proteins (immunology), SARS Virus (genetics), SARS Virus (immunology), Spodoptera, T-Lymphocytes (immunology), Transfection, Viral Vaccines (genetics), Viral Vaccines (immunology).
- MESH :
- chemical , genetics : Antigens, Viral, DNA, Viral, Immunodominant Epitopes, Nucleocapsid Proteins, Recombinant Fusion Proteins, Recombinant Proteins, Viral Vaccines.
- chemical , immunology : Nucleocapsid Proteins, Recombinant Fusion Proteins, Recombinant Proteins, Viral Vaccines.
- genetics : SARS Virus.
- immunology : SARS Virus, T-Lymphocytes.
- Amino Acid Sequence, Animals, Antigen Presentation, Base Sequence, COS Cells, Cell Line, Chlorocebus aethiops, Mice, Microscopy, Immunoelectron, Molecular Sequence Data, Spodoptera, Transfection.
Abstract
Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-gamma and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-gamma responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N76-114, each of which contained nonameric H2d binding domains with high binding scores for both class I and, except for N76-93, class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-gamma and IL-4 responses and strong memory CTL responses to the LAMP-N chimera.
DOI: 10.1016/j.virol.2005.11.042
PubMed: 16387339
Affiliations:
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Tabiin</name></author><author><name sortKey="Sun, Kai" sort="Sun, Kai" uniqKey="Sun K" first="Kai" last="Sun">Kai Sun</name></author><author><name sortKey="Chandrasekaran, Ananth" sort="Chandrasekaran, Ananth" uniqKey="Chandrasekaran A" first="Ananth" last="Chandrasekaran">Ananth Chandrasekaran</name></author><author><name sortKey="Anwar, Azlinda" sort="Anwar, Azlinda" uniqKey="Anwar A" first="Azlinda" last="Anwar">Azlinda Anwar</name></author><author><name sortKey="Yang, Kun" sort="Yang, Kun" uniqKey="Yang K" first="Kun" last="Yang">Kun Yang</name></author><author><name sortKey="Chikhlikar, Priya" sort="Chikhlikar, Priya" uniqKey="Chikhlikar P" first="Priya" last="Chikhlikar">Priya Chikhlikar</name></author><author><name sortKey="Salmon, Jerome" sort="Salmon, Jerome" uniqKey="Salmon J" first="Jerome" last="Salmon">Jerome Salmon</name></author><author><name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name></author><author><name sortKey="Marques, Ernesto T A" sort="Marques, Ernesto T A" uniqKey="Marques E" first="Ernesto T A" last="Marques">Ernesto T A. Marques</name></author><author><name sortKey="Kellathur, Srinivasan N" sort="Kellathur, Srinivasan N" uniqKey="Kellathur S" first="Srinivasan N" last="Kellathur">Srinivasan N. Kellathur</name></author><author><name sortKey="August, Thomas J" sort="August, Thomas J" uniqKey="August T" first="Thomas J" last="August">Thomas J. August</name></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antigen Presentation</term><term>Antigens, Viral (genetics)</term><term>Base Sequence</term><term>COS Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>DNA, Viral (genetics)</term><term>Immunodominant Epitopes (genetics)</term><term>Mice</term><term>Microscopy, Immunoelectron</term><term>Molecular Sequence Data</term><term>Nucleocapsid Proteins (genetics)</term><term>Nucleocapsid Proteins (immunology)</term><term>Recombinant Fusion Proteins (genetics)</term><term>Recombinant Fusion Proteins (immunology)</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (immunology)</term><term>SARS Virus (genetics)</term><term>SARS Virus (immunology)</term><term>Spodoptera</term><term>T-Lymphocytes (immunology)</term><term>Transfection</term><term>Viral Vaccines (genetics)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN viral (génétique)</term><term>Animaux</term><term>Antigènes viraux (génétique)</term><term>Cellules COS</term><term>Données de séquences moléculaires</term><term>Lignée cellulaire</term><term>Lymphocytes T (immunologie)</term><term>Microscopie immunoélectronique</term><term>Protéines de fusion recombinantes (génétique)</term><term>Protéines de fusion recombinantes (immunologie)</term><term>Protéines nucléocapside (génétique)</term><term>Protéines nucléocapside (immunologie)</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (immunologie)</term><term>Présentation d'antigène</term><term>Souris</term><term>Spodoptera</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Transfection</term><term>Vaccins antiviraux (génétique)</term><term>Vaccins antiviraux (immunologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (immunologie)</term><term>Épitopes immunodominants (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term><term>DNA, Viral</term><term>Immunodominant Epitopes</term><term>Nucleocapsid Proteins</term><term>Recombinant Fusion Proteins</term><term>Recombinant Proteins</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Nucleocapsid Proteins</term><term>Recombinant Fusion Proteins</term><term>Recombinant Proteins</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN viral</term><term>Antigènes viraux</term><term>Protéines de fusion recombinantes</term><term>Protéines nucléocapside</term><term>Protéines recombinantes</term><term>Vaccins antiviraux</term><term>Virus du SRAS</term><term>Épitopes immunodominants</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T</term><term>Protéines de fusion recombinantes</term><term>Protéines nucléocapside</term><term>Protéines recombinantes</term><term>Vaccins antiviraux</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antigen Presentation</term><term>Base Sequence</term><term>COS Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Mice</term><term>Microscopy, Immunoelectron</term><term>Molecular Sequence Data</term><term>Spodoptera</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules COS</term><term>Données de séquences moléculaires</term><term>Lignée cellulaire</term><term>Microscopie immunoélectronique</term><term>Présentation d'antigène</term><term>Souris</term><term>Spodoptera</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-gamma and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-gamma responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N76-114, each of which contained nonameric H2d binding domains with high binding scores for both class I and, except for N76-93, class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-gamma and IL-4 responses and strong memory CTL responses to the LAMP-N chimera.</div></front></TEI><affiliations><list><country><li>Singapour</li></country></list><tree><noCountry><name sortKey="Anwar, Azlinda" sort="Anwar, Azlinda" uniqKey="Anwar A" first="Azlinda" last="Anwar">Azlinda Anwar</name><name sortKey="August, Thomas J" sort="August, Thomas J" uniqKey="August T" first="Thomas J" last="August">Thomas J. August</name><name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name><name sortKey="Chandrasekaran, Ananth" sort="Chandrasekaran, Ananth" uniqKey="Chandrasekaran A" first="Ananth" last="Chandrasekaran">Ananth Chandrasekaran</name><name sortKey="Chikhlikar, Priya" sort="Chikhlikar, Priya" uniqKey="Chikhlikar P" first="Priya" last="Chikhlikar">Priya Chikhlikar</name><name sortKey="Kellathur, Srinivasan N" sort="Kellathur, Srinivasan N" uniqKey="Kellathur S" first="Srinivasan N" last="Kellathur">Srinivasan N. Kellathur</name><name sortKey="Marques, Ernesto T A" sort="Marques, Ernesto T A" uniqKey="Marques E" first="Ernesto T A" last="Marques">Ernesto T A. Marques</name><name sortKey="Salmon, Jerome" sort="Salmon, Jerome" uniqKey="Salmon J" first="Jerome" last="Salmon">Jerome Salmon</name><name sortKey="Sun, Kai" sort="Sun, Kai" uniqKey="Sun K" first="Kai" last="Sun">Kai Sun</name><name sortKey="Tabiin, Tani M" sort="Tabiin, Tani M" uniqKey="Tabiin T" first="Tani M" last="Tabiin">Tani M. Tabiin</name><name sortKey="Yang, Kun" sort="Yang, Kun" uniqKey="Yang K" first="Kun" last="Yang">Kun Yang</name></noCountry><country name="Singapour"><noRegion><name sortKey="Gupta, Vandana" sort="Gupta, Vandana" uniqKey="Gupta V" first="Vandana" last="Gupta">Vandana Gupta</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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