Novel pan-DR-binding T cell epitopes of adenovirus induce pro-inflammatory cytokines and chemokines in healthy donors
Identifieur interne : 002D70 ( Main/Exploration ); précédent : 002D69; suivant : 002D71Novel pan-DR-binding T cell epitopes of adenovirus induce pro-inflammatory cytokines and chemokines in healthy donors
Auteurs : Lianne M. Haveman [Pays-Bas, États-Unis] ; Marc Bierings [Pays-Bas] ; Elisabeth Legger [Pays-Bas] ; Mark R. Klein [Pays-Bas, États-Unis] ; Wilco De Jager [Pays-Bas, États-Unis] ; Henny G. Otten [Pays-Bas] ; Salvatore Albani [États-Unis, Italie] ; Wietse Kuis [Pays-Bas] ; Alessandro Sette [États-Unis] ; Berent J. Prakken [Pays-Bas, États-Unis]Source :
- International Immunology [ 0953-8178 ] ; 2006.
Abstract
Adenovirus can cause fatal infections in the immunocompromised host. To date, no effective anti-viral therapy is available. Adoptive therapy with adenovirus-specific T cells could be a promising treatment, but requires the identification of such T cells. Aim of this study was to identify conserved adenoviral T cell epitopes recognized in a majority of healthy individuals. By using a computer algorithm designed to predict pan-HLA-DR-binding T cell epitopes, we selected 19 peptides of adenovirus serotype 5. PBMCs from 26 healthy subjects were isolated and incubated with these peptides to test epitope-specific T cell proliferation. Six epitopes derived from E1B protein, hexon protein (two epitopes), DNA polymerase, E3A glycoprotein and fiber protein induced a proliferative T cell response in the majority of healthy controls. In vitro MHC binding assays confirmed the potential capacity of the adenovirus epitopes to bind multiple MHC alleles. The cytokine and chemokine profile induced by these epitopes was determined with a multiplex immunoassay and revealed a predominant pro-inflammatory pattern. Based on the broad recognition and the induced cytokine and chemokine profile, the detected epitopes can be regarded as potential candidates to select adenovirus-specific T cells for immune intervention in the immunocompromised host.
Url:
DOI: 10.1093/intimm/dxl085
Affiliations:
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Klein</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pediatric Immunology and Hematology, Wilhelmina Children's Hospital, University Medical Center, KC.03.063.0, Lundlaan 6, Postbus 85090, 3508 AB, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>IACOPO Institute, University of California, San Diego, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="De Jager, Wilco" sort="De Jager, Wilco" uniqKey="De Jager W" first="Wilco" last="De Jager">Wilco De Jager</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pediatric Immunology and Hematology, Wilhelmina Children's Hospital, University Medical Center, KC.03.063.0, Lundlaan 6, Postbus 85090, 3508 AB, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>IACOPO Institute, University of California, San Diego, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Otten, Henny G" sort="Otten, Henny G" uniqKey="Otten H" first="Henny G." last="Otten">Henny G. Otten</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Hematology, University Medical Center, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Albani, Salvatore" sort="Albani, Salvatore" uniqKey="Albani S" first="Salvatore" last="Albani">Salvatore Albani</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>IACOPO Institute, University of California, San Diego, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Italie</country><wicri:regionArea>Androclus Therapeutics, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of California, San Diego, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Kuis, Wietse" sort="Kuis, Wietse" uniqKey="Kuis W" first="Wietse" last="Kuis">Wietse Kuis</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pediatric Immunology and Hematology, Wilhelmina Children's Hospital, University Medical Center, KC.03.063.0, Lundlaan 6, Postbus 85090, 3508 AB, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>La Jolla Institute of Allergy and Immunology, San Diego, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation></author><author><name sortKey="Prakken, Berent J" sort="Prakken, Berent J" uniqKey="Prakken B" first="Berent J." last="Prakken">Berent J. Prakken</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pediatric Immunology and Hematology, Wilhelmina Children's Hospital, University Medical Center, KC.03.063.0, Lundlaan 6, Postbus 85090, 3508 AB, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>IACOPO Institute, University of California, San Diego, CA</wicri:regionArea><wicri:noRegion>CA</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Pays-Bas</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">International Immunology</title><idno type="eISSN">1460-2377</idno><idno type="ISSN">0953-8178</idno><imprint><publisher>Oxford University Press</publisher><date>2006</date><date type="e-published">2006</date><biblScope unit="vol">18</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1521">1521</biblScope><biblScope unit="page" to="1529">1529</biblScope></imprint><idno type="ISSN">0953-8178</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-8178</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Adenovirus can cause fatal infections in the immunocompromised host. To date, no effective anti-viral therapy is available. Adoptive therapy with adenovirus-specific T cells could be a promising treatment, but requires the identification of such T cells. Aim of this study was to identify conserved adenoviral T cell epitopes recognized in a majority of healthy individuals. By using a computer algorithm designed to predict pan-HLA-DR-binding T cell epitopes, we selected 19 peptides of adenovirus serotype 5. PBMCs from 26 healthy subjects were isolated and incubated with these peptides to test epitope-specific T cell proliferation. Six epitopes derived from E1B protein, hexon protein (two epitopes), DNA polymerase, E3A glycoprotein and fiber protein induced a proliferative T cell response in the majority of healthy controls. In vitro MHC binding assays confirmed the potential capacity of the adenovirus epitopes to bind multiple MHC alleles. The cytokine and chemokine profile induced by these epitopes was determined with a multiplex immunoassay and revealed a predominant pro-inflammatory pattern. Based on the broad recognition and the induced cytokine and chemokine profile, the detected epitopes can be regarded as potential candidates to select adenovirus-specific T cells for immune intervention in the immunocompromised host.</div></front></TEI><affiliations><list><country><li>Italie</li><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Lombardie</li><li>Utrecht (province)</li></region><settlement><li>Milan</li><li>Utrecht</li></settlement></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Haveman, Lianne M" sort="Haveman, Lianne M" uniqKey="Haveman L" first="Lianne M." last="Haveman">Lianne M. Haveman</name></region><name sortKey="Bierings, Marc" sort="Bierings, Marc" uniqKey="Bierings M" first="Marc" last="Bierings">Marc Bierings</name><name sortKey="De Jager, Wilco" sort="De Jager, Wilco" uniqKey="De Jager W" first="Wilco" last="De Jager">Wilco De Jager</name><name sortKey="Klein, Mark R" sort="Klein, Mark R" uniqKey="Klein M" first="Mark R." last="Klein">Mark R. Klein</name><name sortKey="Kuis, Wietse" sort="Kuis, Wietse" uniqKey="Kuis W" first="Wietse" last="Kuis">Wietse Kuis</name><name sortKey="Legger, Elisabeth" sort="Legger, Elisabeth" uniqKey="Legger E" first="Elisabeth" last="Legger">Elisabeth Legger</name><name sortKey="Otten, Henny G" sort="Otten, Henny G" uniqKey="Otten H" first="Henny G." last="Otten">Henny G. Otten</name><name sortKey="Prakken, Berent J" sort="Prakken, Berent J" uniqKey="Prakken B" first="Berent J." last="Prakken">Berent J. Prakken</name><name sortKey="Prakken, Berent J" sort="Prakken, Berent J" uniqKey="Prakken B" first="Berent J." last="Prakken">Berent J. Prakken</name></country><country name="États-Unis"><noRegion><name sortKey="Haveman, Lianne M" sort="Haveman, Lianne M" uniqKey="Haveman L" first="Lianne M." last="Haveman">Lianne M. Haveman</name></noRegion><name sortKey="Albani, Salvatore" sort="Albani, Salvatore" uniqKey="Albani S" first="Salvatore" last="Albani">Salvatore Albani</name><name sortKey="Albani, Salvatore" sort="Albani, Salvatore" uniqKey="Albani S" first="Salvatore" last="Albani">Salvatore Albani</name><name sortKey="De Jager, Wilco" sort="De Jager, Wilco" uniqKey="De Jager W" first="Wilco" last="De Jager">Wilco De Jager</name><name sortKey="Klein, Mark R" sort="Klein, Mark R" uniqKey="Klein M" first="Mark R." last="Klein">Mark R. Klein</name><name sortKey="Prakken, Berent J" sort="Prakken, Berent J" uniqKey="Prakken B" first="Berent J." last="Prakken">Berent J. Prakken</name><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name></country><country name="Italie"><region name="Lombardie"><name sortKey="Albani, Salvatore" sort="Albani, Salvatore" uniqKey="Albani S" first="Salvatore" last="Albani">Salvatore Albani</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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