Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals
Identifieur interne : 001D98 ( Ncbi/Merge ); précédent : 001D97; suivant : 001D99Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals
Auteurs : Junbao Yang [États-Unis] ; Eddie James [États-Unis] ; Michelle Roti [États-Unis] ; Laurie Huston [États-Unis] ; John A. Gebe [États-Unis] ; William W. Kwok [États-Unis]Source :
- International Immunology [ 0953-8178 ] ; 2008.
Descripteurs français
- KwdFr :
- Animaux, Antigènes d'histocompatibilité de classe II (immunologie), Antigènes d'histocompatibilité de classe II (métabolisme), Cartographie épitopique, Cytokines (biosynthèse), Cytokines (immunologie), Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Glycoprotéines membranaires (métabolisme), Humains, Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (métabolisme), Lymphocytes T CD4+ (virologie), Prolifération cellulaire, Protéines de l'enveloppe virale (immunologie), Protéines de l'enveloppe virale (métabolisme), Souris, Souris transgéniques, Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Syndrome respiratoire aigu sévère (épidémiologie), Séquence d'acides aminés, Virus du SRAS (immunologie), Virus du SRAS (métabolisme), Épitopes immunodominants (immunologie), Épitopes immunodominants (métabolisme).
- MESH :
- biosynthèse : Cytokines.
- immunologie : Antigènes d'histocompatibilité de classe II, Cytokines, Glycoprotéines membranaires, Lymphocytes T CD4+, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Virus du SRAS, Épitopes immunodominants.
- métabolisme : Antigènes d'histocompatibilité de classe II, Glycoprotéines membranaires, Lymphocytes T CD4+, Protéines de l'enveloppe virale, Virus du SRAS, Épitopes immunodominants.
- virologie : Lymphocytes T CD4+, Syndrome respiratoire aigu sévère.
- épidémiologie : Syndrome respiratoire aigu sévère.
- Animaux, Cartographie épitopique, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Humains, Prolifération cellulaire, Souris, Souris transgéniques, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), CD4-Positive T-Lymphocytes (virology), Cell Proliferation, Cytokines (biosynthesis), Cytokines (immunology), Epitope Mapping, Histocompatibility Antigens Class II (immunology), Histocompatibility Antigens Class II (metabolism), Humans, Immunodominant Epitopes (immunology), Immunodominant Epitopes (metabolism), Membrane Glycoproteins (immunology), Membrane Glycoproteins (metabolism), Mice, Mice, Transgenic, Molecular Sequence Data, SARS Virus (immunology), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (epidemiology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (immunology), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , biosynthesis : Cytokines.
- epidemiology : Severe Acute Respiratory Syndrome.
- immunology : CD4-Positive T-Lymphocytes, Cytokines, Histocompatibility Antigens Class II, Immunodominant Epitopes, Membrane Glycoproteins, SARS Virus, Severe Acute Respiratory Syndrome, Viral Envelope Proteins.
- metabolism : CD4-Positive T-Lymphocytes, Histocompatibility Antigens Class II, Immunodominant Epitopes, Membrane Glycoproteins, SARS Virus, Viral Envelope Proteins.
- virology : CD4-Positive T-Lymphocytes, Severe Acute Respiratory Syndrome.
- Amino Acid Sequence, Animals, Cell Proliferation, Epitope Mapping, Humans, Mice, Mice, Transgenic, Molecular Sequence Data, Spike Glycoprotein, Coronavirus.
Abstract
Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong
Url:
DOI: 10.1093/intimm/dxn124
PubMed: 19050106
PubMed Central: 2638843
Links toward previous steps (curation, corpus...)
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- to stream Pmc, to step Curation: 001064
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Links to Exploration step
PMC:2638843Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>CD4-Positive T-Lymphocytes (virology)</term>
<term>Cell Proliferation</term>
<term>Cytokines (biosynthesis)</term>
<term>Cytokines (immunology)</term>
<term>Epitope Mapping</term>
<term>Histocompatibility Antigens Class II (immunology)</term>
<term>Histocompatibility Antigens Class II (metabolism)</term>
<term>Humans</term>
<term>Immunodominant Epitopes (immunology)</term>
<term>Immunodominant Epitopes (metabolism)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Molecular Sequence Data</term>
<term>SARS Virus (immunology)</term>
<term>SARS Virus (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (epidemiology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Antigènes d'histocompatibilité de classe II (immunologie)</term>
<term>Antigènes d'histocompatibilité de classe II (métabolisme)</term>
<term>Cartographie épitopique</term>
<term>Cytokines (biosynthèse)</term>
<term>Cytokines (immunologie)</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T CD4+ (virologie)</term>
<term>Prolifération cellulaire</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Syndrome respiratoire aigu sévère (épidémiologie)</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS (immunologie)</term>
<term>Virus du SRAS (métabolisme)</term>
<term>Épitopes immunodominants (immunologie)</term>
<term>Épitopes immunodominants (métabolisme)</term>
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<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
<term>Épitopes immunodominants</term>
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<term>Immunodominant Epitopes</term>
<term>Membrane Glycoproteins</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Viral Envelope Proteins</term>
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<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes d'histocompatibilité de classe II</term>
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T CD4+</term>
<term>Protéines de l'enveloppe virale</term>
<term>Virus du SRAS</term>
<term>Épitopes immunodominants</term>
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<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Lymphocytes T CD4+</term>
<term>Syndrome respiratoire aigu sévère</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Severe Acute Respiratory Syndrome</term>
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<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cell Proliferation</term>
<term>Epitope Mapping</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Molecular Sequence Data</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Cartographie épitopique</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Prolifération cellulaire</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Séquence d'acides aminés</term>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong <italic>in vitro</italic>
T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed <italic>in vivo</italic>
in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-γ and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.</p>
</div>
</front>
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<author><name sortKey="Roti, Michelle" sort="Roti, Michelle" uniqKey="Roti M" first="Michelle" last="Roti">Michelle Roti</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals</title>
<author><name sortKey="Yang, Junbao" sort="Yang, Junbao" uniqKey="Yang J" first="Junbao" last="Yang">Junbao Yang</name>
<affiliation wicri:level="2"><nlm:aff id="aff1">Benaroya Research Institute at Virginia Mason, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
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<affiliation wicri:level="2"><nlm:aff id="aff1">Benaroya Research Institute at Virginia Mason, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
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<affiliation wicri:level="2"><nlm:aff id="aff1">Benaroya Research Institute at Virginia Mason, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
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<affiliation wicri:level="2"><nlm:aff id="aff1">Benaroya Research Institute at Virginia Mason, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
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<affiliation wicri:level="2"><nlm:aff id="aff1">Benaroya Research Institute at Virginia Mason, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kwok, William W" sort="Kwok, William W" uniqKey="Kwok W" first="William W." last="Kwok">William W. Kwok</name>
<affiliation wicri:level="2"><nlm:aff id="aff1">Benaroya Research Institute at Virginia Mason, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff2">Department of Immunology, University of Washington, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, University of Washington, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
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<orgName type="university">Université de Washington</orgName>
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<series><title level="j">International Immunology</title>
<idno type="ISSN">0953-8178</idno>
<idno type="eISSN">1460-2377</idno>
<imprint><date when="2008">2008</date>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong <italic>in vitro</italic>
T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed <italic>in vivo</italic>
in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-γ and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.</p>
</div>
</front>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals.</title>
<author><name sortKey="Yang, Junbao" sort="Yang, Junbao" uniqKey="Yang J" first="Junbao" last="Yang">Junbao Yang</name>
<affiliation wicri:level="2"><nlm:affiliation>Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="James, Eddie" sort="James, Eddie" uniqKey="James E" first="Eddie" last="James">Eddie James</name>
</author>
<author><name sortKey="Roti, Michelle" sort="Roti, Michelle" uniqKey="Roti M" first="Michelle" last="Roti">Michelle Roti</name>
</author>
<author><name sortKey="Huston, Laurie" sort="Huston, Laurie" uniqKey="Huston L" first="Laurie" last="Huston">Laurie Huston</name>
</author>
<author><name sortKey="Gebe, John A" sort="Gebe, John A" uniqKey="Gebe J" first="John A" last="Gebe">John A. Gebe</name>
</author>
<author><name sortKey="Kwok, William W" sort="Kwok, William W" uniqKey="Kwok W" first="William W" last="Kwok">William W. Kwok</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2009">2009</date>
<idno type="RBID">pubmed:19050106</idno>
<idno type="pmid">19050106</idno>
<idno type="doi">10.1093/intimm/dxn124</idno>
<idno type="wicri:Area/PubMed/Corpus">001A21</idno>
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<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001792</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals.</title>
<author><name sortKey="Yang, Junbao" sort="Yang, Junbao" uniqKey="Yang J" first="Junbao" last="Yang">Junbao Yang</name>
<affiliation wicri:level="2"><nlm:affiliation>Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Benaroya Research Institute at Virginia Mason, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="James, Eddie" sort="James, Eddie" uniqKey="James E" first="Eddie" last="James">Eddie James</name>
</author>
<author><name sortKey="Roti, Michelle" sort="Roti, Michelle" uniqKey="Roti M" first="Michelle" last="Roti">Michelle Roti</name>
</author>
<author><name sortKey="Huston, Laurie" sort="Huston, Laurie" uniqKey="Huston L" first="Laurie" last="Huston">Laurie Huston</name>
</author>
<author><name sortKey="Gebe, John A" sort="Gebe, John A" uniqKey="Gebe J" first="John A" last="Gebe">John A. Gebe</name>
</author>
<author><name sortKey="Kwok, William W" sort="Kwok, William W" uniqKey="Kwok W" first="William W" last="Kwok">William W. Kwok</name>
</author>
</analytic>
<series><title level="j">International immunology</title>
<idno type="eISSN">1460-2377</idno>
<imprint><date when="2009" type="published">2009</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>CD4-Positive T-Lymphocytes (virology)</term>
<term>Cell Proliferation</term>
<term>Cytokines (biosynthesis)</term>
<term>Cytokines (immunology)</term>
<term>Epitope Mapping</term>
<term>Histocompatibility Antigens Class II (immunology)</term>
<term>Histocompatibility Antigens Class II (metabolism)</term>
<term>Humans</term>
<term>Immunodominant Epitopes (immunology)</term>
<term>Immunodominant Epitopes (metabolism)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Molecular Sequence Data</term>
<term>SARS Virus (immunology)</term>
<term>SARS Virus (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (epidemiology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Antigènes d'histocompatibilité de classe II (immunologie)</term>
<term>Antigènes d'histocompatibilité de classe II (métabolisme)</term>
<term>Cartographie épitopique</term>
<term>Cytokines (biosynthèse)</term>
<term>Cytokines (immunologie)</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T CD4+ (virologie)</term>
<term>Prolifération cellulaire</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Syndrome respiratoire aigu sévère (épidémiologie)</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS (immunologie)</term>
<term>Virus du SRAS (métabolisme)</term>
<term>Épitopes immunodominants (immunologie)</term>
<term>Épitopes immunodominants (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes d'histocompatibilité de classe II</term>
<term>Cytokines</term>
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T CD4+</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
<term>Épitopes immunodominants</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Cytokines</term>
<term>Histocompatibility Antigens Class II</term>
<term>Immunodominant Epitopes</term>
<term>Membrane Glycoproteins</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Histocompatibility Antigens Class II</term>
<term>Immunodominant Epitopes</term>
<term>Membrane Glycoproteins</term>
<term>SARS Virus</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes d'histocompatibilité de classe II</term>
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T CD4+</term>
<term>Protéines de l'enveloppe virale</term>
<term>Virus du SRAS</term>
<term>Épitopes immunodominants</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Lymphocytes T CD4+</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cell Proliferation</term>
<term>Epitope Mapping</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Molecular Sequence Data</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cartographie épitopique</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Prolifération cellulaire</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Séquence d'acides aminés</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159-171, 166-178, 449-461 and 1083-1097 were identified to contain naturally processed immunodominant epitopes based on strong in vitro T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed in vivo in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-gamma and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.</div>
</front>
</TEI>
</pubmed>
</double>
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