Dendritic cells at a DNA vaccination site express the encoded influenza nucleoprotein and prime MHC class I-restricted cytolytic lymphocytes upon adoptive transfer.
Intradermal inoculation of plasmids expressing antigens that contain MHC class I-restricted epitopes leads to the induction of specific CD8(+) cytotoxic T lymphocytes (CTL). The role of in situ transfected antigen-presenting cells (APC) in the priming of specific CTL subsequent to intradermal DNA immunization was investigated using a plasmid (NPV1) expressing the nucleoprotein (NP) of influenza virus that contains a nuclear targeting signal and a dominant class I/K(d)-restricted epitope. Inoculation of NPV1 leads to in situ transfection of MHC class II(+) and class II(-) cells, as revealed by the nuclear localization of NP. Between 2 and 3% of MHC class II(+) and class II(-) cells with the ability to migrate out of the epidermis expressed NP. Upon adoptive transfer into naive recipients, class II(+) migratory cells recovered from the area inoculated with NP-expressing plasmid were significantly superior regarding the ability to prime virus-specific CTL as compared to MHC class II(-) cells. Together, these results are consistent with the role of local dendritic cells loaded with antigen in the priming of CTL by intradermal DNA immunization.
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Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
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Inaba
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Steinman
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Bona
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D019264:Adoptive Transfer; D000818:Animals; D003713:Dendritic Cells / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009975:Orthomyxoviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics*
D015395:Histocompatibility Antigens Class I; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins