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dc.contributor.authorVitalis, Timothy Z.
dc.contributor.authorZhang, Qian-Jin
dc.contributor.authorAlimonti, Judie
dc.contributor.authorChen, Susan S.
dc.contributor.authorBasha, Genc
dc.contributor.authorMoise, Alexander R.
dc.contributor.authorTiong, Jacqueline
dc.contributor.authorTian, Mei Mei
dc.contributor.authorBok Choi, Kyung
dc.contributor.authorWaterfield, Douglas
dc.contributor.authorJeffries, Andy
dc.contributor.authorJefferies, Wilfred A.
dc.date.accessioned2015-05-11T16:30:42Z
dc.date.available2015-05-11T16:30:42Z
dc.date.issued2005-12-30
dc.identifier.citationVitalis TZ, Zhang Q-J, Alimonti J, Chen SS, Basha G, Moise A, et al. (2005) Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant. PLoS Pathog 1(4): e36. http://www.dx.doi.org/10.1371/journal.ppat.0010036en_US
dc.identifier.urihttp://hdl.handle.net/1808/17685
dc.descriptionThis is the publisher's version, also available electronically from "journals.plos.org".en_US
dc.description.abstractWe 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.en_US
dc.publisherPublic Library of Scienceen_US
dc.titleUsing the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvanten_US
dc.typeArticle
kusw.kuauthorVitalis, Timothy Z.
kusw.kuauthorMoise, Alexander R.
kusw.kuauthorJefferies, Wilfred A.
kusw.kudepartmentPharmacology & Toxicologyen_US
dc.identifier.doi10.1371/journal.ppat.0010036
dc.identifier.orcidhttps://orcid.org/0000-0003-2307-6035
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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