Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve1
Identifieur interne : 000392 ( Ncbi/Curation ); précédent : 000391; suivant : 000393Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve1
Auteurs : Carla Oseroff [États-Unis] ; Bjoern Peters [États-Unis] ; Valerie Pasquetto ; Magdalini Moutaftsi [États-Unis] ; John Sidney [États-Unis] ; Vijay Panchanathan [Australie] ; David C. Tscharke [Australie] ; Bernard Maillere [France] ; Howard Grey [États-Unis] ; Alessandro Sette [États-Unis]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2008.
Abstract
Understanding immunity to vaccinia virus (VACV) is important for the development of safer vaccines for smallpox- and poxvirus-vectored recombinant vaccines. VACV is also emerging as an outstanding model for studying CD8+ T cell immunodominance because of the large number of CD8+ T cell epitopes known for this virus in both mice and humans. In this study, we characterize the CD8+ T cell response in vaccinated BALB/c mice by a genome-wide mapping approach. Responses to each of 54 newly identified H-2d-restricted T cell epitopes could be detected after i.p. and dermal vaccination routes. Analysis of these new epitopes in the context of those already known for VACV in mice and humans revealed two important findings. First, CD8+ T cell epitopes are not randomly distributed across the VACV proteome, with some proteins being poorly or nonimmunogenic, while others are immunoprevalent, being frequently recognized across diverse MHC haplotypes. Second, some proteins constituted the major targets of the immune response by a specific haplotype as they recruited the majority of the specific CD8+ T cells but these proteins did not correspond to the immunoprevalent Ags. Thus, we found a dissociation between immunoprevalence and immunodominance, implying that different sets of rules govern these two phenomena. Together, these findings have clear implications for the design of CD8+ T cell subunit vaccines and in particular raise the exciting prospect of being able to choose subunits without reference to MHC restriction.
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PubMed: 18490718
PubMed Central: 2533852
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Peters</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Pasquetto, Valerie" sort="Pasquetto, Valerie" uniqKey="Pasquetto V" first="Valerie" last="Pasquetto">Valerie Pasquetto</name></author><author><name sortKey="Moutaftsi, Magdalini" sort="Moutaftsi, Magdalini" uniqKey="Moutaftsi M" first="Magdalini" last="Moutaftsi">Magdalini Moutaftsi</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region 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Australian Capital Territory, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory</wicri:regionArea><wicri:noRegion>Australian Capital Territory</wicri:noRegion></affiliation></author><author><name sortKey="Tscharke, David C" sort="Tscharke, David C" uniqKey="Tscharke D" first="David C." last="Tscharke">David C. Tscharke</name><affiliation wicri:level="1"><nlm:aff id="A2"> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea> School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australian Capital Territory</wicri:regionArea><wicri:noRegion>Australian Capital Territory</wicri:noRegion></affiliation></author><author><name sortKey="Maillere, Bernard" sort="Maillere, Bernard" uniqKey="Maillere B" first="Bernard" last="Maillere">Bernard Maillere</name><affiliation wicri:level="3"><nlm:aff id="A3"> Institut de Biologie et Technologies de Saclay, Service d’Ingénierie Moléculaire des Protéines, Commissariat à l’Energie Atomique-Saclay, Gif sur Yvette, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Institut de Biologie et Technologies de Saclay, Service d’Ingénierie Moléculaire des Protéines, Commissariat à l’Energie Atomique-Saclay, Gif sur Yvette</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Gif-sur-Yvette</settlement></placeName></affiliation></author><author><name sortKey="Grey, Howard" sort="Grey, Howard" uniqKey="Grey H" first="Howard" last="Grey">Howard Grey</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name><affiliation wicri:level="2"><nlm:aff id="A1"> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea> Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla</wicri:cityArea></affiliation></author></analytic><series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title><idno type="ISSN">0022-1767</idno><idno type="eISSN">1550-6606</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Understanding immunity to vaccinia virus (VACV) is important for the development of safer vaccines for smallpox- and poxvirus-vectored recombinant vaccines. VACV is also emerging as an outstanding model for studying CD8<sup>+</sup> T cell immunodominance because of the large number of CD8<sup>+</sup> T cell epitopes known for this virus in both mice and humans. In this study, we characterize the CD8<sup>+</sup> T cell response in vaccinated BALB/c mice by a genome-wide mapping approach. Responses to each of 54 newly identified H-2<sup>d</sup>-restricted T cell epitopes could be detected after i.p. and dermal vaccination routes. Analysis of these new epitopes in the context of those already known for VACV in mice and humans revealed two important findings. First, CD8<sup>+</sup> T cell epitopes are not randomly distributed across the VACV proteome, with some proteins being poorly or nonimmunogenic, while others are immunoprevalent, being frequently recognized across diverse MHC haplotypes. Second, some proteins constituted the major targets of the immune response by a specific haplotype as they recruited the majority of the specific CD8<sup>+</sup> T cells but these proteins did not correspond to the immunoprevalent Ags. Thus, we found a dissociation between immunoprevalence and immunodominance, implying that different sets of rules govern these two phenomena. Together, these findings have clear implications for the design of CD8<sup>+</sup> T cell subunit vaccines and in particular raise the exciting prospect of being able to choose subunits without reference to MHC restriction.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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