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Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant
dc.contributor.author | Vitalis, Timothy Z. | |
dc.contributor.author | Zhang, Qian-Jin | |
dc.contributor.author | Alimonti, Judie | |
dc.contributor.author | Chen, Susan S. | |
dc.contributor.author | Basha, Genc | |
dc.contributor.author | Moise, Alexander R. | |
dc.contributor.author | Tiong, Jacqueline | |
dc.contributor.author | Tian, Mei Mei | |
dc.contributor.author | Bok Choi, Kyung | |
dc.contributor.author | Waterfield, Douglas | |
dc.contributor.author | Jeffries, Andy | |
dc.contributor.author | Jefferies, Wilfred A. | |
dc.date.accessioned | 2015-05-11T16:30:42Z | |
dc.date.available | 2015-05-11T16:30:42Z | |
dc.date.issued | 2005-12-30 | |
dc.identifier.citation | Vitalis 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.0010036 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17685 | |
dc.description | This is the publisher's version, also available electronically from "journals.plos.org". | en_US |
dc.description.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. | en_US |
dc.publisher | Public Library of Science | en_US |
dc.title | Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant | en_US |
dc.type | Article | |
kusw.kuauthor | Vitalis, Timothy Z. | |
kusw.kuauthor | Moise, Alexander R. | |
kusw.kuauthor | Jefferies, Wilfred A. | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.1371/journal.ppat.0010036 | |
dc.identifier.orcid | https://orcid.org/0000-0003-2307-6035 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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Pharmacy Scholarly Works [299]