Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant
Identifieur interne : 001191 ( Pmc/Checkpoint ); précédent : 001190; suivant : 001192Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant
Auteurs : Timothy Z. Vitalis [Canada] ; Qian-Jin Zhang [Canada] ; Judie Alimonti [Canada] ; Susan S. Chen [Canada] ; Genc Basha [Canada] ; Alex Moise [Canada] ; Jacqueline Tiong [Canada] ; Mei Mei Tian [Canada] ; Kyung Bok Choi [Canada] ; Douglas Waterfield [Canada] ; Andy Jeffries [Canada] ; Wilfred A. Jefferies [Canada]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2005.
Abstract
We hypothesize that over-expression of transporters associated with antigen processing (TAP1 and TAP2), components of the major histocompatibility complex (MHC) class I antigen-processing pathway, enhances antigen-specific cytotoxic activity in response to viral infection. An expression system using recombinant vaccinia virus (VV) was used to over-express human TAP1 and TAP2 (VV-hTAP1,2) in normal mice. Mice coinfected with either vesicular stomatitis virus plus VV-hTAP1,2 or Sendai virus plus VV-hTAP1,2 increased cytotoxic lymphocyte (CTL) activity by at least 4-fold when compared to coinfections with a control vector, VV encoding the plasmid PJS-5. Coinfections with VV-hTAP1,2 increased virus-specific CTL precursors compared to control infections without VV-hTAP1,2. In an animal model of lethal viral challenge after vaccination, VV-hTAP1,2 provided protection against a lethal challenge of VV at doses 100-fold lower than control vector alone. Mechanistically, the total MHC class I antigen surface expression and the cross-presentation mechanism in spleen-derived dendritic cells was augmented by over-expression of TAP. Furthermore, VV-hTAP1,2 increases splenic TAP transport activity and endogenous antigen processing, thus rendering infected targets more susceptible to CTL recognition and subsequent killing. This is the first demonstration that over-expression of a component of the antigen-processing machinery increases endogenous antigen presentation and dendritic cell cross-presentation of exogenous antigens and may provide a novel and general approach for increasing immune responses against pathogens at low doses of vaccine inocula.
Url:
DOI: 10.1371/journal.ppat.0010036
PubMed: 16389301
PubMed Central: 1323471
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:1323471Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant</title><author><name sortKey="Vitalis, Timothy Z" sort="Vitalis, Timothy Z" uniqKey="Vitalis T" first="Timothy Z" last="Vitalis">Timothy Z. Vitalis</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Zhang, Qian Jin" sort="Zhang, Qian Jin" uniqKey="Zhang Q" first="Qian-Jin" last="Zhang">Qian-Jin Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Alimonti, Judie" sort="Alimonti, Judie" uniqKey="Alimonti J" first="Judie" last="Alimonti">Judie Alimonti</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Chen, Susan S" sort="Chen, Susan S" uniqKey="Chen S" first="Susan S" last="Chen">Susan S. Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Zoology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Basha, Genc" sort="Basha, Genc" uniqKey="Basha G" first="Genc" last="Basha">Genc Basha</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Moise, Alex" sort="Moise, Alex" uniqKey="Moise A" first="Alex" last="Moise">Alex Moise</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Zoology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Tiong, Jacqueline" sort="Tiong, Jacqueline" uniqKey="Tiong J" first="Jacqueline" last="Tiong">Jacqueline Tiong</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Tian, Mei Mei" sort="Tian, Mei Mei" uniqKey="Tian M" first="Mei Mei" last="Tian">Mei Mei Tian</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Choi, Kyung Bok" sort="Choi, Kyung Bok" uniqKey="Choi K" first="Kyung Bok" last="Choi">Kyung Bok Choi</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Waterfield, Douglas" sort="Waterfield, Douglas" uniqKey="Waterfield D" first="Douglas" last="Waterfield">Douglas Waterfield</name><affiliation wicri:level="1"><nlm:aff id="aff5"> Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Jeffries, Andy" sort="Jeffries, Andy" uniqKey="Jeffries A" first="Andy" last="Jeffries">Andy Jeffries</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Zoology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">16389301</idno><idno type="pmc">1323471</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1323471</idno><idno type="RBID">PMC:1323471</idno><idno type="doi">10.1371/journal.ppat.0010036</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">001411</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001411</idno><idno type="wicri:Area/Pmc/Curation">001411</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001411</idno><idno type="wicri:Area/Pmc/Checkpoint">001191</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001191</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant</title><author><name sortKey="Vitalis, Timothy Z" sort="Vitalis, Timothy Z" uniqKey="Vitalis T" first="Timothy Z" last="Vitalis">Timothy Z. Vitalis</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Zhang, Qian Jin" sort="Zhang, Qian Jin" uniqKey="Zhang Q" first="Qian-Jin" last="Zhang">Qian-Jin Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Alimonti, Judie" sort="Alimonti, Judie" uniqKey="Alimonti J" first="Judie" last="Alimonti">Judie Alimonti</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Chen, Susan S" sort="Chen, Susan S" uniqKey="Chen S" first="Susan S" last="Chen">Susan S. Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Zoology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Basha, Genc" sort="Basha, Genc" uniqKey="Basha G" first="Genc" last="Basha">Genc Basha</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Moise, Alex" sort="Moise, Alex" uniqKey="Moise A" first="Alex" last="Moise">Alex Moise</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Zoology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Tiong, Jacqueline" sort="Tiong, Jacqueline" uniqKey="Tiong J" first="Jacqueline" last="Tiong">Jacqueline Tiong</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Tian, Mei Mei" sort="Tian, Mei Mei" uniqKey="Tian M" first="Mei Mei" last="Tian">Mei Mei Tian</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Choi, Kyung Bok" sort="Choi, Kyung Bok" uniqKey="Choi K" first="Kyung Bok" last="Choi">Kyung Bok Choi</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Waterfield, Douglas" sort="Waterfield, Douglas" uniqKey="Waterfield D" first="Douglas" last="Waterfield">Douglas Waterfield</name><affiliation wicri:level="1"><nlm:aff id="aff5"> Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Jeffries, Andy" sort="Jeffries, Andy" uniqKey="Jeffries A" first="Andy" last="Jeffries">Andy Jeffries</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><affiliation wicri:level="1"><nlm:aff id="aff1"> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Zoology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We hypothesize that over-expression of transporters associated with antigen processing (TAP1 and TAP2), components of the major histocompatibility complex (MHC) class I antigen-processing pathway, enhances antigen-specific cytotoxic activity in response to viral infection. An expression system using recombinant vaccinia virus (VV) was used to over-express human TAP1 and TAP2 (VV-hTAP1,2) in normal mice. Mice coinfected with either vesicular stomatitis virus plus VV-hTAP1,2 or Sendai virus plus VV-hTAP1,2 increased cytotoxic lymphocyte (CTL) activity by at least 4-fold when compared to coinfections with a control vector, VV encoding the plasmid PJS-5. Coinfections with VV-hTAP1,2 increased virus-specific CTL precursors compared to control infections without VV-hTAP1,2. In an animal model of lethal viral challenge after vaccination, VV-hTAP1,2 provided protection against a lethal challenge of VV at doses 100-fold lower than control vector alone. Mechanistically, the total MHC class I antigen surface expression and the cross-presentation mechanism in spleen-derived dendritic cells was augmented by over-expression of TAP. Furthermore, VV-hTAP1,2 increases splenic TAP transport activity and endogenous antigen processing, thus rendering infected targets more susceptible to CTL recognition and subsequent killing. This is the first demonstration that over-expression of a component of the antigen-processing machinery increases endogenous antigen presentation and dendritic cell cross-presentation of exogenous antigens and may provide a novel and general approach for increasing immune responses against pathogens at low doses of vaccine inocula.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zinkernagel, Rm" uniqKey="Zinkernagel R">RM Zinkernagel</name></author><author><name sortKey="Doherty, Pc" uniqKey="Doherty P">PC Doherty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Townsend, Ar" uniqKey="Townsend A">AR Townsend</name></author><author><name sortKey="Rothbard, J" uniqKey="Rothbard J">J Rothbard</name></author><author><name sortKey="Gotch, Fm" uniqKey="Gotch F">FM Gotch</name></author><author><name sortKey="Bahadur, G" uniqKey="Bahadur G">G Bahadur</name></author><author><name sortKey="Wraith, D" uniqKey="Wraith D">D Wraith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suh, Wk" uniqKey="Suh W">WK Suh</name></author><author><name sortKey="Cohen Doyle, Mf" uniqKey="Cohen Doyle M">MF Cohen-Doyle</name></author><author><name sortKey="Fruh, K" uniqKey="Fruh K">K Fruh</name></author><author><name sortKey="Wang, K" uniqKey="Wang K">K Wang</name></author><author><name sortKey="Peterson, Pa" uniqKey="Peterson P">PA Peterson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frisan, T" uniqKey="Frisan T">T Frisan</name></author><author><name sortKey="Zhang, Qj" uniqKey="Zhang Q">QJ Zhang</name></author><author><name sortKey="Levitskaya, J" uniqKey="Levitskaya J">J Levitskaya</name></author><author><name sortKey="Coram, M" uniqKey="Coram M">M Coram</name></author><author><name sortKey="Kurilla, Mg" uniqKey="Kurilla M">MG Kurilla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alimonti, J" uniqKey="Alimonti J">J Alimonti</name></author><author><name sortKey="Zhang, Qj" uniqKey="Zhang Q">QJ Zhang</name></author><author><name sortKey="Gabathuler, R" uniqKey="Gabathuler R">R Gabathuler</name></author><author><name sortKey="Reid, G" uniqKey="Reid G">G Reid</name></author><author><name sortKey="Chen, Ss" uniqKey="Chen S">SS Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deverson, Ev" uniqKey="Deverson E">EV Deverson</name></author><author><name sortKey="Gow, Ir" uniqKey="Gow I">IR Gow</name></author><author><name sortKey="Coadwell, Wj" uniqKey="Coadwell W">WJ Coadwell</name></author><author><name sortKey="Monaco, Jj" uniqKey="Monaco J">JJ Monaco</name></author><author><name sortKey="Butcher, Gw" uniqKey="Butcher G">GW Butcher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelly, A" uniqKey="Kelly A">A Kelly</name></author><author><name sortKey="Powis, Sh" uniqKey="Powis S">SH Powis</name></author><author><name sortKey="Glynne, R" uniqKey="Glynne R">R Glynne</name></author><author><name sortKey="Radley, E" uniqKey="Radley E">E Radley</name></author><author><name sortKey="Beck, S" uniqKey="Beck S">S Beck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Norbury, Cc" uniqKey="Norbury C">CC Norbury</name></author><author><name sortKey="Princiotta, Mf" uniqKey="Princiotta M">MF Princiotta</name></author><author><name sortKey="Bacik, I" uniqKey="Bacik I">I Bacik</name></author><author><name sortKey="Brutkiewicz, Rr" uniqKey="Brutkiewicz R">RR Brutkiewicz</name></author><author><name sortKey="Wood, P" uniqKey="Wood P">P Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ortmann, B" uniqKey="Ortmann B">B Ortmann</name></author><author><name sortKey="Androlewicz, Mj" uniqKey="Androlewicz M">MJ Androlewicz</name></author><author><name sortKey="Cresswell, P" uniqKey="Cresswell P">P Cresswell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belyakov, Im" uniqKey="Belyakov I">IM Belyakov</name></author><author><name sortKey="Earl, P" uniqKey="Earl P">P Earl</name></author><author><name sortKey="Dzutsev, A" uniqKey="Dzutsev A">A Dzutsev</name></author><author><name sortKey="Kuznetsov, Va" uniqKey="Kuznetsov V">VA Kuznetsov</name></author><author><name sortKey="Lemon, M" uniqKey="Lemon M">M Lemon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, H" uniqKey="Takahashi H">H Takahashi</name></author><author><name sortKey="Takeshita, T" uniqKey="Takeshita T">T Takeshita</name></author><author><name sortKey="Morein, B" uniqKey="Morein B">B Morein</name></author><author><name sortKey="Putney, S" uniqKey="Putney S">S Putney</name></author><author><name sortKey="Germain, Rn" uniqKey="Germain R">RN Germain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salter, Rd" uniqKey="Salter R">RD Salter</name></author><author><name sortKey="Cresswell, P" uniqKey="Cresswell P">P Cresswell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spies, T" uniqKey="Spies T">T Spies</name></author><author><name sortKey="Demars, R" uniqKey="Demars R">R DeMars</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Gl" uniqKey="Smith G">GL Smith</name></author><author><name sortKey="Symons, Ja" uniqKey="Symons J">JA Symons</name></author><author><name sortKey="Khanna, A" uniqKey="Khanna A">A Khanna</name></author><author><name sortKey="Vanderplasschen, A" uniqKey="Vanderplasschen A">A Vanderplasschen</name></author><author><name sortKey="Alcami, A" uniqKey="Alcami A">A Alcami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hooper, Jw" uniqKey="Hooper J">JW Hooper</name></author><author><name sortKey="Custer, Dm" uniqKey="Custer D">DM Custer</name></author><author><name sortKey="Schmaljohn, Cs" uniqKey="Schmaljohn C">CS Schmaljohn</name></author><author><name sortKey="Schmaljohn, Al" uniqKey="Schmaljohn A">AL Schmaljohn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brandt, Ta" uniqKey="Brandt T">TA Brandt</name></author><author><name sortKey="Jacobs, Bl" uniqKey="Jacobs B">BL Jacobs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smee, Df" uniqKey="Smee D">DF Smee</name></author><author><name sortKey="Bailey, Kw" uniqKey="Bailey K">KW Bailey</name></author><author><name sortKey="Sidwell, Rw" uniqKey="Sidwell R">RW Sidwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reading, Pc" uniqKey="Reading P">PC Reading</name></author><author><name sortKey="Smith, Gl" uniqKey="Smith G">GL Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bellone, M" uniqKey="Bellone M">M Bellone</name></author><author><name sortKey="Iezzi, G" uniqKey="Iezzi G">G Iezzi</name></author><author><name sortKey="Manfredi, Aa" uniqKey="Manfredi A">AA Manfredi</name></author><author><name sortKey="Protti, Mp" uniqKey="Protti M">MP Protti</name></author><author><name sortKey="Dellabona, P" uniqKey="Dellabona P">P Dellabona</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Momburg, F" uniqKey="Momburg F">F Momburg</name></author><author><name sortKey="Neefjes, Jj" uniqKey="Neefjes J">JJ Neefjes</name></author><author><name sortKey="Hammerling, Gj" uniqKey="Hammerling G">GJ Hammerling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uebel, S" uniqKey="Uebel S">S Uebel</name></author><author><name sortKey="Meyer, Th" uniqKey="Meyer T">TH Meyer</name></author><author><name sortKey="Kraas, W" uniqKey="Kraas W">W Kraas</name></author><author><name sortKey="Kienle, S" uniqKey="Kienle S">S Kienle</name></author><author><name sortKey="Jung, G" uniqKey="Jung G">G Jung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Motta, I" uniqKey="Motta I">I Motta</name></author><author><name sortKey="Lone, Yc" uniqKey="Lone Y">YC Lone</name></author><author><name sortKey="Kourilsky, P" uniqKey="Kourilsky P">P Kourilsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Armandola, Ea" uniqKey="Armandola E">EA Armandola</name></author><author><name sortKey="Momburg, F" uniqKey="Momburg F">F Momburg</name></author><author><name sortKey="Nijenhuis, M" uniqKey="Nijenhuis M">M Nijenhuis</name></author><author><name sortKey="Bulbuc, N" uniqKey="Bulbuc N">N Bulbuc</name></author><author><name sortKey="Fruh, K" uniqKey="Fruh K">K Fruh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Endert, Pm" uniqKey="Van Endert P">PM van Endert</name></author><author><name sortKey="Riganelli, D" uniqKey="Riganelli D">D Riganelli</name></author><author><name sortKey="Greco, G" uniqKey="Greco G">G Greco</name></author><author><name sortKey="Fleischhauer, K" uniqKey="Fleischhauer K">K Fleischhauer</name></author><author><name sortKey="Sidney, J" uniqKey="Sidney J">J Sidney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Momburg, F" uniqKey="Momburg F">F Momburg</name></author><author><name sortKey="Roelse, J" uniqKey="Roelse J">J Roelse</name></author><author><name sortKey="Howard, Jc" uniqKey="Howard J">JC Howard</name></author><author><name sortKey="Butcher, Gw" uniqKey="Butcher G">GW Butcher</name></author><author><name sortKey="Hammerling, Gj" uniqKey="Hammerling G">GJ Hammerling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lizee, G" uniqKey="Lizee G">G Lizee</name></author><author><name sortKey="Basha, G" uniqKey="Basha G">G Basha</name></author><author><name sortKey="Tiong, J" uniqKey="Tiong J">J Tiong</name></author><author><name sortKey="Julien, Jp" uniqKey="Julien J">JP Julien</name></author><author><name sortKey="Tian, M" uniqKey="Tian M">M Tian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guermonprez, P" uniqKey="Guermonprez P">P Guermonprez</name></author><author><name sortKey="Saveanu, L" uniqKey="Saveanu L">L Saveanu</name></author><author><name sortKey="Kleijmeer, M" uniqKey="Kleijmeer M">M Kleijmeer</name></author><author><name sortKey="Davoust, J" uniqKey="Davoust J">J Davoust</name></author><author><name sortKey="Van Endert, P" uniqKey="Van Endert P">P Van Endert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Jondal, M" uniqKey="Jondal M">M Jondal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Jondal, M" uniqKey="Jondal M">M Jondal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seliger, B" uniqKey="Seliger B">B Seliger</name></author><author><name sortKey="Wollscheid, U" uniqKey="Wollscheid U">U Wollscheid</name></author><author><name sortKey="Momburg, F" uniqKey="Momburg F">F Momburg</name></author><author><name sortKey="Blankenstein, T" uniqKey="Blankenstein T">T Blankenstein</name></author><author><name sortKey="Huber, C" uniqKey="Huber C">C Huber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reits, Ea" uniqKey="Reits E">EA Reits</name></author><author><name sortKey="Vos, Jc" uniqKey="Vos J">JC Vos</name></author><author><name sortKey="Gromme, M" uniqKey="Gromme M">M Gromme</name></author><author><name sortKey="Neefjes, J" uniqKey="Neefjes J">J Neefjes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bacik, I" uniqKey="Bacik I">I Bacik</name></author><author><name sortKey="Cox, Jh" uniqKey="Cox J">JH Cox</name></author><author><name sortKey="Anderson, R" uniqKey="Anderson R">R Anderson</name></author><author><name sortKey="Yewdell, Jw" uniqKey="Yewdell J">JW Yewdell</name></author><author><name sortKey="Bennink, Jr" uniqKey="Bennink J">JR Bennink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ackerman, Al" uniqKey="Ackerman A">AL Ackerman</name></author><author><name sortKey="Kyritsis, C" uniqKey="Kyritsis C">C Kyritsis</name></author><author><name sortKey="Tampe, R" uniqKey="Tampe R">R Tampe</name></author><author><name sortKey="Cresswell, P" uniqKey="Cresswell P">P Cresswell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Houde, M" uniqKey="Houde M">M Houde</name></author><author><name sortKey="Bertholet, S" uniqKey="Bertholet S">S Bertholet</name></author><author><name sortKey="Gagnon, E" uniqKey="Gagnon E">E Gagnon</name></author><author><name sortKey="Brunet, S" uniqKey="Brunet S">S Brunet</name></author><author><name sortKey="Goyette, G" uniqKey="Goyette G">G Goyette</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Melnick, Jl" uniqKey="Melnick J">JL Melnick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dertzbaugh, Mt" uniqKey="Dertzbaugh M">MT Dertzbaugh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singh, M" uniqKey="Singh M">M Singh</name></author><author><name sortKey="O Hagan, D" uniqKey="O Hagan D">D O'Hagan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kahn, P" uniqKey="Kahn P">P Kahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russ, G" uniqKey="Russ G">G Russ</name></author><author><name sortKey="Esquivel, F" uniqKey="Esquivel F">F Esquivel</name></author><author><name sortKey="Yewdell, Jw" uniqKey="Yewdell J">JW Yewdell</name></author><author><name sortKey="Cresswell, P" uniqKey="Cresswell P">P Cresswell</name></author><author><name sortKey="Spies, T" uniqKey="Spies T">T Spies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Norbury, Cc" uniqKey="Norbury C">CC Norbury</name></author><author><name sortKey="Princiotta, Mf" uniqKey="Princiotta M">MF Princiotta</name></author><author><name sortKey="Bacik, I" uniqKey="Bacik I">I Bacik</name></author><author><name sortKey="Brutkiewicz, Rr" uniqKey="Brutkiewicz R">RR Brutkiewicz</name></author><author><name sortKey="Wood, P" uniqKey="Wood P">P Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Androlewicz, Mj" uniqKey="Androlewicz M">MJ Androlewicz</name></author><author><name sortKey="Anderson, Ks" uniqKey="Anderson K">KS Anderson</name></author><author><name sortKey="Cresswell, P" uniqKey="Cresswell P">P Cresswell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heemels, Mt" uniqKey="Heemels M">MT Heemels</name></author><author><name sortKey="Schumacher, Tn" uniqKey="Schumacher T">TN Schumacher</name></author><author><name sortKey="Wonigeit, K" uniqKey="Wonigeit K">K Wonigeit</name></author><author><name sortKey="Ploegh, Hl" uniqKey="Ploegh H">HL Ploegh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Porgador, A" uniqKey="Porgador A">A Porgador</name></author><author><name sortKey="Yewdell, Jw" uniqKey="Yewdell J">JW Yewdell</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y Deng</name></author><author><name sortKey="Bennink, Jr" uniqKey="Bennink J">JR Bennink</name></author><author><name sortKey="Germain, Rn" uniqKey="Germain R">RN Germain</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">ppat</journal-id><journal-id journal-id-type="publisher-id">plpa</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">16389301</article-id><article-id pub-id-type="pmc">1323471</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.0010036</article-id><article-id pub-id-type="publisher-id">05-PLPA-RA-0130R2</article-id><article-id pub-id-type="sici">plpa-01-04-05</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Biotechnology</subject><subject>Cell Biology</subject><subject>Epidemiology - Public Health</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Microbiology</subject><subject>Pathology</subject><subject>Virology</subject></subj-group><subj-group subj-group-type="System Taxonomy"><subject>Homo (Human)</subject><subject>Mus (Mouse)</subject><subject>Viruses</subject></subj-group></article-categories><title-group><article-title>Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant</article-title><alt-title alt-title-type="running-head">A New Paradigm in Vaccination</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Vitalis</surname><given-names>Timothy Z</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Qian-Jin</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="author-notes" rid="n104">¤a</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Alimonti</surname><given-names>Judie</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="author-notes" rid="n105">¤b</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Susan S</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Basha</surname><given-names>Genc</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Moise</surname><given-names>Alex</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="author-notes" rid="n106">¤c</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Tiong</surname><given-names>Jacqueline</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Tian</surname><given-names>Mei Mei</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Kyung Bok</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Waterfield</surname><given-names>Douglas</given-names></name><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Jeffries</surname><given-names>Andy</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Jefferies</surname><given-names>Wilfred A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="aff" rid="aff1"></xref></contrib></contrib-group><aff id="aff1"><label>1</label> The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada</aff><aff id="aff2"><label>2</label> Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada</aff><aff id="aff3"><label>3</label> Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada</aff><aff id="aff4"><label>4</label> Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada</aff><aff id="aff5"><label>5</label> Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada</aff><aff id="aff6"><label>6</label> Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</aff><contrib-group><contrib contrib-type="editor"><name><surname>Manchester</surname><given-names>Marianne</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">Scripps Research Institute, United States of America</aff><author-notes><corresp id="cor1">* To whom correspondence should be addressed. E-mail: <email>wilf@brc.ubc.ca</email></corresp><fn id="n104" fn-type="current-aff"><p>¤a Current address: Cellular Biology and Anatomy, LSU Health Sciences Center, Shreveport, Louisiana, United States of America</p></fn><fn id="n105" fn-type="current-aff"><p>¤b Current address: Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada</p></fn><fn id="n106" fn-type="current-aff"><p>¤c Current address: Case Western Reserve University, Cleveland, Ohio, United States of America</p></fn></author-notes><pub-date pub-type="ppub"><month>12</month><year>2005</year></pub-date><pub-date pub-type="epub"><day>30</day><month>12</month><year>2005</year></pub-date><volume>1</volume><issue>4</issue><elocation-id>e36</elocation-id><history><date date-type="received"><day>15</day><month>8</month><year>2005</year></date><date date-type="accepted"><day>25</day><month>10</month><year>2005</year></date></history><permissions><copyright-statement>Copyright: © 2005 Vitalis et al.</copyright-statement><copyright-year>2005</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>We hypothesize that over-expression of transporters associated with antigen processing (TAP1 and TAP2), components of the major histocompatibility complex (MHC) class I antigen-processing pathway, enhances antigen-specific cytotoxic activity in response to viral infection. An expression system using recombinant vaccinia virus (VV) was used to over-express human TAP1 and TAP2 (VV-hTAP1,2) in normal mice. Mice coinfected with either vesicular stomatitis virus plus VV-hTAP1,2 or Sendai virus plus VV-hTAP1,2 increased cytotoxic lymphocyte (CTL) activity by at least 4-fold when compared to coinfections with a control vector, VV encoding the plasmid PJS-5. Coinfections with VV-hTAP1,2 increased virus-specific CTL precursors compared to control infections without VV-hTAP1,2. In an animal model of lethal viral challenge after vaccination, VV-hTAP1,2 provided protection against a lethal challenge of VV at doses 100-fold lower than control vector alone. Mechanistically, the total MHC class I antigen surface expression and the cross-presentation mechanism in spleen-derived dendritic cells was augmented by over-expression of TAP. Furthermore, VV-hTAP1,2 increases splenic TAP transport activity and endogenous antigen processing, thus rendering infected targets more susceptible to CTL recognition and subsequent killing. This is the first demonstration that over-expression of a component of the antigen-processing machinery increases endogenous antigen presentation and dendritic cell cross-presentation of exogenous antigens and may provide a novel and general approach for increasing immune responses against pathogens at low doses of vaccine inocula.</p></abstract><abstract abstract-type="synopsis"><title>Synopsis</title><p>The development of protective vaccines against infectious diseases such as AIDS, SARS, and West Nile virus has become a societal priority but remains a scientific challenge. In recent years, the threat of bioterrorism agents such as anthrax and smallpox has heightened the need for the rapid development of effective new vaccines. One of the major stumbling blocks to the implementation of any vaccine is the toxic side effects on the vaccine candidate. For example, a significant number of doses of a new vaccine against smallpox have been commissioned, but approximately 20% of the individuals targeted to be inoculated will suffer toxicity due to vaccination. Furthermore, an additional difficulty in the production of vaccines is the creation of sufficient doses to vaccinate a large population. The authors have identified a novel approach that appears to address these issues. They demonstrate that the inclusion, in low doses of vaccines, of a normal component of the antigen-processing pathway, the transporter associated with antigen processing (TAP), confers protective immunity against lethal viral loads during viral challenges. This new paradigm is shown to be applicable to many viruses, including poxviruses, and could significantly advance the creation of new vaccines and improve those that already exist.</p></abstract><counts><page-count count="10"></page-count></counts><custom-meta-group><custom-meta><meta-name>Citation:</meta-name><meta-value>Vitalis TZ, Zhang QJ, Alimonti J, Chen SS, Basha G, et al. (2005) Using the TAP component of the antigen-processing machinery as a molecular adjuvant. PLoS Pathog 1(4): e36.</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Vitalis, Timothy Z" sort="Vitalis, Timothy Z" uniqKey="Vitalis T" first="Timothy Z" last="Vitalis">Timothy Z. Vitalis</name></noRegion><name sortKey="Alimonti, Judie" sort="Alimonti, Judie" uniqKey="Alimonti J" first="Judie" last="Alimonti">Judie Alimonti</name><name sortKey="Alimonti, Judie" sort="Alimonti, Judie" uniqKey="Alimonti J" first="Judie" last="Alimonti">Judie Alimonti</name><name sortKey="Alimonti, Judie" sort="Alimonti, Judie" uniqKey="Alimonti J" first="Judie" last="Alimonti">Judie Alimonti</name><name sortKey="Basha, Genc" sort="Basha, Genc" uniqKey="Basha G" first="Genc" last="Basha">Genc Basha</name><name sortKey="Basha, Genc" sort="Basha, Genc" uniqKey="Basha G" first="Genc" last="Basha">Genc Basha</name><name sortKey="Chen, Susan S" sort="Chen, Susan S" uniqKey="Chen S" first="Susan S" last="Chen">Susan S. Chen</name><name sortKey="Chen, Susan S" sort="Chen, Susan S" uniqKey="Chen S" first="Susan S" last="Chen">Susan S. Chen</name><name sortKey="Chen, Susan S" sort="Chen, Susan S" uniqKey="Chen S" first="Susan S" last="Chen">Susan S. Chen</name><name sortKey="Choi, Kyung Bok" sort="Choi, Kyung Bok" uniqKey="Choi K" first="Kyung Bok" last="Choi">Kyung Bok Choi</name><name sortKey="Choi, Kyung Bok" sort="Choi, Kyung Bok" uniqKey="Choi K" first="Kyung Bok" last="Choi">Kyung Bok Choi</name><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><name sortKey="Jefferies, Wilfred A" sort="Jefferies, Wilfred A" uniqKey="Jefferies W" first="Wilfred A" last="Jefferies">Wilfred A. Jefferies</name><name sortKey="Jeffries, Andy" sort="Jeffries, Andy" uniqKey="Jeffries A" first="Andy" last="Jeffries">Andy Jeffries</name><name sortKey="Jeffries, Andy" sort="Jeffries, Andy" uniqKey="Jeffries A" first="Andy" last="Jeffries">Andy Jeffries</name><name sortKey="Moise, Alex" sort="Moise, Alex" uniqKey="Moise A" first="Alex" last="Moise">Alex Moise</name><name sortKey="Moise, Alex" sort="Moise, Alex" uniqKey="Moise A" first="Alex" last="Moise">Alex Moise</name><name sortKey="Moise, Alex" sort="Moise, Alex" uniqKey="Moise A" first="Alex" last="Moise">Alex Moise</name><name sortKey="Tian, Mei Mei" sort="Tian, Mei Mei" uniqKey="Tian M" first="Mei Mei" last="Tian">Mei Mei Tian</name><name sortKey="Tian, Mei Mei" sort="Tian, Mei Mei" uniqKey="Tian M" first="Mei Mei" last="Tian">Mei Mei Tian</name><name sortKey="Tian, Mei Mei" sort="Tian, Mei Mei" uniqKey="Tian M" first="Mei Mei" last="Tian">Mei Mei Tian</name><name sortKey="Tiong, Jacqueline" sort="Tiong, Jacqueline" uniqKey="Tiong J" first="Jacqueline" last="Tiong">Jacqueline Tiong</name><name sortKey="Tiong, Jacqueline" sort="Tiong, Jacqueline" uniqKey="Tiong J" first="Jacqueline" last="Tiong">Jacqueline Tiong</name><name sortKey="Tiong, Jacqueline" sort="Tiong, Jacqueline" uniqKey="Tiong J" first="Jacqueline" last="Tiong">Jacqueline Tiong</name><name sortKey="Vitalis, Timothy Z" sort="Vitalis, Timothy Z" uniqKey="Vitalis T" first="Timothy Z" last="Vitalis">Timothy Z. Vitalis</name><name sortKey="Waterfield, Douglas" sort="Waterfield, Douglas" uniqKey="Waterfield D" first="Douglas" last="Waterfield">Douglas Waterfield</name><name sortKey="Zhang, Qian Jin" sort="Zhang, Qian Jin" uniqKey="Zhang Q" first="Qian-Jin" last="Zhang">Qian-Jin Zhang</name><name sortKey="Zhang, Qian Jin" sort="Zhang, Qian Jin" uniqKey="Zhang Q" first="Qian-Jin" last="Zhang">Qian-Jin Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001191 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 001191 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Pmc
|étape= Checkpoint
|type= RBID
|clé= PMC:1323471
|texte= Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:16389301" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |