Using the TAP Component of the Antigen-Processing Machinery as a Molecular Adjuvant
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Issue Date
2005-12-30Author
Vitalis, Timothy Z.
Zhang, Qian-Jin
Alimonti, Judie
Chen, Susan S.
Basha, Genc
Moise, Alexander R.
Tiong, Jacqueline
Tian, Mei Mei
Bok Choi, Kyung
Waterfield, Douglas
Jeffries, Andy
Jefferies, Wilfred A.
Publisher
Public Library of Science
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
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.
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This is the publisher's version, also available electronically from "journals.plos.org".
Collections
- Pharmacy Scholarly Works [293]
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
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