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Departments of
*
Microbiology and
Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996;
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261; and
§
Center for Cellular and Genetic Therapy, Department of Surgery, Duke University, Durham, NC 27710
Immunization with plasmid DNA holds promise as a vaccination strategy perhaps useful in situations that currently lack vaccines, since the major means of immune induction may differ from more conventional approach. In the present study, we demonstrate that exposure of macrophages to plasmid DNA encoding viral proteins or OVA generates Ag-specific material that, when presented in vitro by dendritic cells to naive T cells, induces primary CTL response or elicits IL-2 production from an OVA peptide-specific T-T hybridoma. The immunogenic material released was proteinaceous in nature, free of apoptotic bodies, and had an apparent m.w. much larger than a 9–11-aa CTL-recognizable peptide. The macrophage-released factor(s) specifically required a hydrolyzable ATP substrate and was inhibited by procedures that removed or hydrolyzed ATP; in addition, anti-heat-shock protein 70 antiserum abrogated the activity to a large extent. These results indicate the possible involvement of a heat-shock protein 70-linked peptide chaperone in a cross-priming method of immune induction by DNA vaccination. Such a cross-priming process may represent a principal mechanism by which plasmid DNA delivered to cells such as myocytes effectively shuttle Ag to DC or other APC to achieve CTL induction in vivo.
This article has been cited by other articles:
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  M. Chen, C. Barnfield, T. I. Naslund, M. N. Fleeton, and P. Liljestrom MyD88 Expression Is Required for Efficient Cross-Presentation of Viral Antigens from Infected Cells J. Virol., March 1, 2005; 79(5): 2964 - 2972. [Abstract] [Full Text] [PDF]
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 R. Schirmbeck, N. Fissolo, P. Chaplin, and J. Reimann Enhanced Priming of Multispecific, Murine CD8+ T Cell Responses by DNA Vaccines Expressing Stress Protein-Binding Polytope Peptides J. Immunol., August 1, 2003; 171(3): 1240 - 1246. [Abstract] [Full Text] [PDF]
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 J. Stebbing, B. Gazzard, L. Kim, S. Portsmouth, A. Wildfire, I. Teo, M. Nelson, M. Bower, F. Gotch, S. Shaunak, et al. The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors Blood, May 15, 2003; 101(10): 4000 - 4004. [Abstract] [Full Text] [PDF]
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 U. Kumaraguru, C. D. Pack, and B. T. Rouse Toll-like receptor ligand links innate and adaptive immune responses by the production of heat-shock proteins J. Leukoc. Biol., May 1, 2003; 73(5): 574 - 583. [Abstract] [Full Text] [PDF]
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C. Rush, T. Mitchell, and P. Garside Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways J. Immunol., November 1, 2002; 169(9): 4951 - 4960. [Abstract] [Full Text] [PDF]
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R. Kammerer, D. Stober, P. Riedl, C. Oehninger, R. Schirmbeck, and J. Reimann Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells J. Immunol., January 1, 2002; 168(1): 108 - 117. [Abstract] [Full Text] [PDF]
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J. H. Cho, J. W. Youn, and Y. C. Sung Cross-Priming as a Predominant Mechanism for Inducing CD8+ T Cell Responses in Gene Gun DNA Immunization J. Immunol., November 15, 2001; 167(10): 5549 - 5557. [Abstract] [Full Text] [PDF]
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S. K. Eo, U. Kumaraguru, and B. T. Rouse Plasmid DNA Encoding CCR7 Ligands Compensate for Dysfunctional CD8+ T Cell Responses by Effects on Dendritic Cells J. Immunol., October 1, 2001; 167(7): 3592 - 3599. [Abstract] [Full Text] [PDF]
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S. K. Eo, M. Gierynska, A. A. Kamar, and B. T. Rouse Prime-Boost Immunization with DNA Vaccine: Mucosal Route of Administration Changes the Rules J. Immunol., May 1, 2001; 166(9): 5473 - 5479. [Abstract] [Full Text] [PDF]
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S. K. Eo, S. Lee, S. Chun, and B. T. Rouse Modulation of Immunity against Herpes Simplex Virus Infection via Mucosal Genetic Transfer of Plasmid DNA Encoding Chemokines J. Virol., January 15, 2001; 75(2): 569 - 578. [Abstract] [Full Text]
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U. Kumaraguru, I. A. Davis, S. Deshpande, S. S. Tevethia, and B. T. Rouse Lymphotoxin {{alpha}}-/- Mice Develop Functionally Impaired CD8+ T Cell Responses and Fail to Contain Virus Infection of the Central Nervous System J. Immunol., January 15, 2001; 166(2): 1066 - 1074. [Abstract] [Full Text] [PDF]
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