Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations.
Identifieur interne : 003252 ( PubMed/Corpus ); précédent : 003251; suivant : 003253Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations.
Auteurs : Brenna J. Hill ; Patricia A. Darrah ; Zachary Ende ; David R. Ambrozak ; Kylie M. Quinn ; Sam Darko ; Emma Gostick ; Linda Wooldridge ; Hugo A. Van Den Berg ; Vanessa Venturi ; Martin Larsen ; Miles P. Davenport ; Robert A. Seder ; David A. Price ; Daniel C. DouekSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2014.
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-2K(d) 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(d) 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(d) 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.
DOI: 10.4049/jimmunol.1401017
PubMed: 25348625
Links to Exploration step
pubmed:25348625Le document en format XML
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<author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A" last="Price">David A. Price</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations.</title>
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</affiliation>
</author>
<author><name sortKey="Ende, Zachary" sort="Ende, Zachary" uniqKey="Ende Z" first="Zachary" last="Ende">Zachary Ende</name>
<affiliation><nlm:affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</nlm:affiliation>
</affiliation>
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<author><name sortKey="Ambrozak, David R" sort="Ambrozak, David R" uniqKey="Ambrozak D" first="David R" last="Ambrozak">David R. Ambrozak</name>
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</affiliation>
</author>
<author><name sortKey="Quinn, Kylie M" sort="Quinn, Kylie M" uniqKey="Quinn K" first="Kylie M" last="Quinn">Kylie M. Quinn</name>
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</affiliation>
</author>
<author><name sortKey="Darko, Sam" sort="Darko, Sam" uniqKey="Darko S" first="Sam" last="Darko">Sam Darko</name>
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</affiliation>
</author>
<author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name>
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<author><name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name>
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</affiliation>
</author>
<author><name sortKey="Larsen, Martin" sort="Larsen, Martin" uniqKey="Larsen M" first="Martin" last="Larsen">Martin Larsen</name>
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</affiliation>
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<author><name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P" last="Davenport">Miles P. Davenport</name>
<affiliation><nlm:affiliation>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Seder, Robert A" sort="Seder, Robert A" uniqKey="Seder R" first="Robert A" last="Seder">Robert A. Seder</name>
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</affiliation>
</author>
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<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="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>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
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<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>
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<front><div type="abstract" xml:lang="en">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(d) 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(d) 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(d) 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.</div>
</front>
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<Title>Journal of immunology (Baltimore, Md. : 1950)</Title>
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<ArticleTitle>Epitope specificity delimits the functional capabilities of vaccine-induced CD8 T cell populations.</ArticleTitle>
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<Abstract><AbstractText>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(d) 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(d) 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(d) 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.</AbstractText>
<CopyrightInformation>Copyright © 2014 by The American Association of Immunologists, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hill</LastName>
<ForeName>Brenna J</ForeName>
<Initials>BJ</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Darrah</LastName>
<ForeName>Patricia A</ForeName>
<Initials>PA</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ende</LastName>
<ForeName>Zachary</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Ambrozak</LastName>
<ForeName>David R</ForeName>
<Initials>DR</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Quinn</LastName>
<ForeName>Kylie M</ForeName>
<Initials>KM</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Darko</LastName>
<ForeName>Sam</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Gostick</LastName>
<ForeName>Emma</ForeName>
<Initials>E</Initials>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Wooldridge</LastName>
<ForeName>Linda</ForeName>
<Initials>L</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van den Berg</LastName>
<ForeName>Hugo A</ForeName>
<Initials>HA</Initials>
<AffiliationInfo><Affiliation>Mathematics Institute, University of Warwick, Coventry CV4 7AL, United Kingdom;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Venturi</LastName>
<ForeName>Vanessa</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Larsen</LastName>
<ForeName>Martin</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, F-75013 Paris, France; and Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), CR7, F-75013 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Davenport</LastName>
<ForeName>Miles P</ForeName>
<Initials>MP</Initials>
<AffiliationInfo><Affiliation>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington 2052, New South Wales, Australia;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Seder</LastName>
<ForeName>Robert A</ForeName>
<Initials>RA</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Price</LastName>
<ForeName>David A</ForeName>
<Initials>DA</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom; ddouek@mail.nih.gov priced6@cardiff.ac.uk.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Douek</LastName>
<ForeName>Daniel C</ForeName>
<Initials>DC</Initials>
<AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ddouek@mail.nih.gov priced6@cardiff.ac.uk.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>100326</GrantID>
<Agency>Wellcome Trust</Agency>
<Country>United Kingdom</Country>
</Grant>
<Grant><Agency>Intramural NIH HHS</Agency>
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