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Protein-Immunostimulatory DNA-Conjugate

A Novel Immunogen

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Abstract

The original finding made by Tokunaga and colleagues (1,2) demonstrated that DNA from Mycobacterium bovis Bacillus Calmette Guérin has antitumor activities and induces natural killer (NK) cells to secrete interferon-γ (IFN-γ). Over the last 10 yr, this finding has stimulated much research on the immunostimulatory properties of bacterial DNA. It was shown that bacterial immunostimulatory DNA sequences (ISS) consist of palindromic sequences of the motif purine-purine-CpG-pyrimidine-pyrimidine (3,4). This motif occurs about 20 times more often in bacterial DNA than in mammalian DNA (5). Furthermore, the cytosine of the crucial CpG sequence in ISS is usually methylated in mammalian DNA and methylated CpG motifs do not show the immuno-stimulatory properties of ISS (6). ISS not only activate NK cells to secrete IFN-γ, but also activate both murine and human antigen presenting cells (APC) to secrete type 1 cytokines such as, IFN-a, β, IL-6, IL-12, and IL-18 (4,7,8), which direct the immune response toward a Th 1 immune response. ISS also induce costimulatory molecules on APC (9) and cause human B-cell proliferation and IgM secretion (10). Another property of ISS is the ability to induce “cross-priming,” the phenomenon of priming CD8+ cytotoxic lymphocytes (CTL) against foreign protein antigens (11,12).

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© 2002 Humana Press Inc., Totowa, NJ

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Takabayashi, K., Tighe, H., Beck, L., Spiegelberg, H.L. (2002). Protein-Immunostimulatory DNA-Conjugate. In: Raz, E. (eds) Microbial DNA and Host Immunity. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-305-7_14

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  • DOI: https://doi.org/10.1007/978-1-59259-305-7_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9728-1

  • Online ISBN: 978-1-59259-305-7

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