Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations
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Auteurs : Brenna J. Hill [États-Unis] ; Patricia A. Darrah [États-Unis] ; Zachary Ende [États-Unis] ; David R. Ambrozak [États-Unis] ; Kylie M. Quinn [États-Unis] ; Sam Darko [États-Unis] ; Emma Gostick [Royaume-Uni] ; Linda Wooldridge [Royaume-Uni] ; Hugo A. Van Den Berg [Royaume-Uni] ; Vanessa Venturi [Australie] ; Martin Larsen [France] ; Miles P. Davenport [Australie] ; Robert A. Seder [États-Unis] ; David A. Price [États-Unis, Royaume-Uni] ; Daniel C. Douek [États-Unis]Source :
- The Journal of Immunology Author Choice [ 0022-1767 ] ; 2014.
Descripteurs français
- KwdFr :
- Adenoviridae (génétique), Animaux, Antigène d'histocompatibilité H2-D (métabolisme), Antigènes H-2 (métabolisme), Cellules cultivées, Cytotoxicité immunologique, Femelle, Humains, Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (virologie), Mémoire immunologique, Produits du gène gag du virus de l'immunodéficience humaine (génétique), Produits du gène gag du virus de l'immunodéficience humaine (métabolisme), Produits du gène pol du virus de l'immunodéficience humaine (génétique), Produits du gène pol du virus de l'immunodéficience humaine (métabolisme), Souris, Souris de lignée BALB C, Vaccination, Vaccins contre le SIDA, Vecteurs génétiques, Épitopes immunodominants (génétique), Épitopes immunodominants (métabolisme).
- MESH :
- génétique : Adenoviridae, Produits du gène gag du virus de l'immunodéficience humaine, Produits du gène pol du virus de l'immunodéficience humaine, Épitopes immunodominants.
- immunologie : Lymphocytes T CD8+.
- métabolisme : Antigène d'histocompatibilité H2-D, Antigènes H-2, Produits du gène gag du virus de l'immunodéficience humaine, Produits du gène pol du virus de l'immunodéficience humaine, Épitopes immunodominants.
- virologie : Lymphocytes T CD8+.
- Animaux, Cellules cultivées, Cytotoxicité immunologique, Femelle, Humains, Mémoire immunologique, Souris, Souris de lignée BALB C, Vaccination, Vaccins contre le SIDA, Vecteurs génétiques.
English descriptors
- KwdEn :
- AIDS Vaccines, Adenoviridae (genetics), Animals, CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (virology), Cells, Cultured, Cytotoxicity, Immunologic, Female, Genetic Vectors, H-2 Antigens (metabolism), Histocompatibility Antigen H-2D (metabolism), Humans, Immunodominant Epitopes (genetics), Immunodominant Epitopes (metabolism), Immunologic Memory, Mice, Mice, Inbred BALB C, Vaccination, gag Gene Products, Human Immunodeficiency Virus (genetics), gag Gene Products, Human Immunodeficiency Virus (metabolism), pol Gene Products, Human Immunodeficiency Virus (genetics), pol Gene Products, Human Immunodeficiency Virus (metabolism).
- MESH :
- chemical , genetics : Immunodominant Epitopes, gag Gene Products, Human Immunodeficiency Virus, pol Gene Products, Human Immunodeficiency Virus.
- chemical , metabolism : H-2 Antigens, Histocompatibility Antigen H-2D, Immunodominant Epitopes, gag Gene Products, Human Immunodeficiency Virus, pol Gene Products, Human Immunodeficiency Virus.
- chemical : AIDS Vaccines.
- genetics : Adenoviridae.
- immunology : CD8-Positive T-Lymphocytes.
- virology : CD8-Positive T-Lymphocytes.
- Animals, Cells, Cultured, Cytotoxicity, Immunologic, Female, Genetic Vectors, Humans, Immunologic Memory, Mice, Mice, Inbred BALB C, Vaccination.
Abstract
Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.
Url:
DOI: 10.4049/jimmunol.1401017
PubMed: 25348625
PubMed Central: 4238745
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Hill</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Darrah, Patricia A" sort="Darrah, Patricia A" uniqKey="Darrah P" first="Patricia A." last="Darrah">Patricia A. Darrah</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Ende, Zachary" sort="Ende, Zachary" uniqKey="Ende Z" first="Zachary" last="Ende">Zachary Ende</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Ambrozak, David R" sort="Ambrozak, David R" uniqKey="Ambrozak D" first="David R." last="Ambrozak">David R. Ambrozak</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Quinn, Kylie M" sort="Quinn, Kylie M" uniqKey="Quinn K" first="Kylie M." last="Quinn">Kylie M. Quinn</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Darko, Sam" sort="Darko, Sam" uniqKey="Darko S" first="Sam" last="Darko">Sam Darko</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN</wicri:regionArea><wicri:noRegion>Cardiff CF14 4XN</wicri:noRegion></affiliation></author><author><name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name><affiliation wicri:level="1"><nlm:aff id="aff3">Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol BS8 1TD</wicri:regionArea><wicri:noRegion>Bristol BS8 1TD</wicri:noRegion></affiliation></author><author><name sortKey="Van Den Berg, Hugo A" sort="Van Den Berg, Hugo A" uniqKey="Van Den Berg H" first="Hugo A." last="Van Den Berg">Hugo A. Van Den Berg</name><affiliation wicri:level="1"><nlm:aff id="aff4">Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Mathematics Institute, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name><affiliation wicri:level="1"><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Larsen, Martin" sort="Larsen, Martin" uniqKey="Larsen M" first="Martin" last="Larsen">Martin Larsen</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff6">INSERM, U1135, Centre d’Immunologie et des Maladies Infectieuses, F-75013 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1135, Centre d’Immunologie et des Maladies Infectieuses, F-75013 Paris</wicri:regionArea><wicri:noRegion>75013 Paris</wicri:noRegion><wicri:noRegion>75013 Paris</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Centre d’Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d’Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris</wicri:regionArea><wicri:noRegion>75013 Paris</wicri:noRegion><wicri:noRegion>75013 Paris</wicri:noRegion></affiliation></author><author><name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name><affiliation wicri:level="1"><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Seder, Robert A" sort="Seder, Robert A" uniqKey="Seder R" first="Robert A." last="Seder">Robert A. Seder</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN</wicri:regionArea><wicri:noRegion>Cardiff CF14 4XN</wicri:noRegion></affiliation></author><author><name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name><affiliation wicri:level="2"><nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author></analytic><series><title level="j">The Journal of Immunology Author Choice</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIDS Vaccines</term><term>Adenoviridae (genetics)</term><term>Animals</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>CD8-Positive T-Lymphocytes (virology)</term><term>Cells, Cultured</term><term>Cytotoxicity, Immunologic</term><term>Female</term><term>Genetic Vectors</term><term>H-2 Antigens (metabolism)</term><term>Histocompatibility Antigen H-2D (metabolism)</term><term>Humans</term><term>Immunodominant Epitopes (genetics)</term><term>Immunodominant Epitopes (metabolism)</term><term>Immunologic Memory</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Vaccination</term><term>gag Gene Products, Human Immunodeficiency Virus (genetics)</term><term>gag Gene Products, Human Immunodeficiency Virus (metabolism)</term><term>pol Gene Products, Human Immunodeficiency Virus (genetics)</term><term>pol Gene Products, Human Immunodeficiency Virus (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adenoviridae (génétique)</term><term>Animaux</term><term>Antigène d'histocompatibilité H2-D (métabolisme)</term><term>Antigènes H-2 (métabolisme)</term><term>Cellules cultivées</term><term>Cytotoxicité immunologique</term><term>Femelle</term><term>Humains</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Lymphocytes T CD8+ (virologie)</term><term>Mémoire immunologique</term><term>Produits du gène gag du virus de l'immunodéficience humaine (génétique)</term><term>Produits du gène gag du virus de l'immunodéficience humaine (métabolisme)</term><term>Produits du gène pol du virus de l'immunodéficience humaine (génétique)</term><term>Produits du gène pol du virus de l'immunodéficience humaine (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Vaccination</term><term>Vaccins contre le SIDA</term><term>Vecteurs génétiques</term><term>Épitopes immunodominants (génétique)</term><term>Épitopes immunodominants (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Immunodominant Epitopes</term><term>gag Gene Products, Human Immunodeficiency Virus</term><term>pol Gene Products, Human Immunodeficiency Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>H-2 Antigens</term><term>Histocompatibility Antigen H-2D</term><term>Immunodominant Epitopes</term><term>gag Gene Products, Human Immunodeficiency Virus</term><term>pol Gene Products, Human Immunodeficiency Virus</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>AIDS Vaccines</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adenoviridae</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adenoviridae</term><term>Produits du gène gag du virus de l'immunodéficience humaine</term><term>Produits du gène pol du virus de l'immunodéficience humaine</term><term>Épitopes immunodominants</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T CD8+</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène d'histocompatibilité H2-D</term><term>Antigènes H-2</term><term>Produits du gène gag du virus de l'immunodéficience humaine</term><term>Produits du gène pol du virus de l'immunodéficience humaine</term><term>Épitopes immunodominants</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Lymphocytes T CD8+</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>Cytotoxicity, Immunologic</term><term>Female</term><term>Genetic Vectors</term><term>Humans</term><term>Immunologic Memory</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Cytotoxicité immunologique</term><term>Femelle</term><term>Humains</term><term>Mémoire immunologique</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Vaccination</term><term>Vaccins contre le SIDA</term><term>Vecteurs génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2K<sup>d</sup> epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2D<sup>d</sup> epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2D<sup>d</sup> specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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