Synthetic Oligonucleotides with Particular Base Sequences from the cDNA Encoding Proteins of Mycobacterium bovis BCG Induce Interferons and Activate Natural Killer Cells

@article{Tokunaga1992SyntheticOW,
  title={Synthetic Oligonucleotides with Particular Base Sequences from the cDNA Encoding Proteins of Mycobacterium bovis BCG Induce Interferons and Activate Natural Killer Cells},
  author={Tohru Tokunaga and Osamu Yano and Etsuro Kuramoto and Yoshimitsu Kimura and Toshiko Yamamoto and Tetsuro Kataoka and Saburo Yamamoto},
  journal={Microbiology and Immunology},
  year={1992},
  volume={36}
}
Thirteen kinds of 45‐mer single‐stranded oligonucleotide, having sequence randomly selected from the known cDNA encoding BCG proteins, were tested for their capability to augment natural killer (NK) cell activity of mouse spleen cells in vitro. Six out of the 13 oligonucleotides showed the activity, while the others did not. In order to know the minimal and essential sequence(s) responsible for the biological activity, 2 kinds of 30‐mer and 5 kinds of 15‐mer oligonucleotide fragments of an… 
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Antitumor Activity of Synthetic Oligonucleotides with Sequences from cDNA Encoding Proteins of Mycobacterium bovis BCG
TLDR
Results suggested that palindromic structure is essential for the antitumor activity of the synthetic oligonucleotides.
Oligonucleotide Sequences Required for Natural Killer Cell Activation
TLDR
The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5 ‐CG‐3 motif(s), and the size and the number of Palindromes showed the strongest activity among the oligonucleotides tested.
CpG‐containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: A new class of vaccine adjuvants
TLDR
It is shown that CpG‐containing oligonucleotides represent a powerful adjuvant for both humoral and cellular immune responses and may serve as inexpensive and safe vaccine adjuvants and, in addition, differential effects due to sequence may allow for directed responses.
DNA from Bacteria, but Not from Vertebrates, Induces Interferons, Activates Natural Killer Cells and Inhibits Tumor Growth
TLDR
The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified and it was shown that the factor to activate macrophages was interferon (IFN)‐gamma and that to inhibit viral growth was IFN‐alpha/beta.
Historical Perspectives
TLDR
The response of higher animals against immunostimulatory DNA must be the most primitive but important mechanism for self-nonself discrimination against foreign DNA.
The influence of DNA sequence on the immunostimulatory properties of plasmid DNA vectors.
TLDR
The results suggest that the addition of 20 to 60-base dG sequences to plasmids does not significantly affect their properties as immunostimulators or vaccines and suggest that MSR ligands can block cytokine induction by plasmid DNA whether or not theplasmid contains extended runs of dG.
The influence of base sequence on the immunological properties of defined oligonucleotides.
Activation of NK cell (human and mouse) by immunostimulatory DNA sequence
TLDR
Antitumor activity of MY-1 was also abolished if the animals were pretreated with asialo GM1 antiserum or carrageenan suggesting that the activity can be ascribed mainly to activated NK cells [16].
Binding of oligoguanylate to scavenger receptors is required for oligonucleotides to augment NK cell activity and induce IFN.
TLDR
It is suggested that the binding of an extrapalindromic sequence to the scavenger receptor is required for the immunostimulatory activity of oligo-1, a 30mer single-stranded oligonucleotide with oligoG sequences next to the active palindromo-G sequences.
Inhibition of a C‐rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice
TLDR
Results showed that a C‐rich MTODN, designated MT01, was able to inhibit the proliferation of human peripheral blood mononuclear cells induced by cytosine–phosphate–guanosine (CpG) oligodeoxynucleotides (ODNs) and the production of type I interferon from human PBMCs stimulated by TLR agonists.
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References

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In vitro Augmentation of Natural Killer Cell Activity and Production of Interferon‐α/β and ‐γ with Deoxyribonucleic Acid Fraction from Mycobacterium bovis BCG
A nucleic acid‐rich fraction extracted and purified from BCG (MY‐1) augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factor(s) which showed anti‐viral activity…
A SYNTHETIC SINGLE‐STRANDED DNA, POLY(dG, dC), INDUCES TNTERFERON‐α/β AND ‐γ, AUGMENTS NATURAL KILLER ACTIVITY, AND SUPPRESSES TUMOR GROWTH
TLDR
Direct cytotoxicity of poly(dG, dC) at a concentration of 1,000 μg/ml against IMC cells was not observed in vitro, and the virus‐inhibitory activity of the supernatant was mostly neutralized by anti‐IFNα/β.
In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG.
TLDR
Antitumor activities of MY-1 were also abolished if the animals were pretreated with anti-asialo GM1 antiserum or carrageenan, suggesting that the activities can be ascribed mainly to activated NK cells.
Characterization, Sequence Determination, and Immunogenicity of a 64-Kilodalton Protein of Mycobacterium bovis BCG Expressed in Escherichia coli K-12
TLDR
The DNA sequence of a previously cloned Mycobacterium bovis BCG gene encoding an immunogenic 64-kilodalton protein, MbaA, is reported, supporting the previously observed strong reactivity of human T-cell clones with this, for mycobacteria, common antigen.
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TLDR
The gene for the extracellular alpha antigen of Mycobacterium bovis BCG was cloned by using a single probe restricted to G or C in the third position, and it was revealed that the alpha antigen gene encoded 323 amino acid residues, including 40 amino acids for signal peptide followed by 283 amino acids by mature protein.
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TLDR
Western blots (immunoblots) showed that this cloned protein was recognized by sera from M. bovis-infected cattle, although not all cattle with bovine tuberculosis produced antibodies reactive to this clone.
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TLDR
The NK activity in all of seven patients with gastric cancer, 12 patients with colonic cancer, and six patients with uterine cancer was augmented by incubation with Mycobacterium bovis BCG, although the degree of augmentation varied depending upon the origin of PBL.
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TLDR
A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid, was found to possess strong antitumor activity, suggesting that the DNA from BCG possessed strong antitUMor activity under certain conditions.
In Situ Infiltration of Natural Killer‐Like Cells Induced by Intradermal Injection of the Nucleic Acid Fraction from BCG
TLDR
Results indicate that the nucleic acid components of MY‐1 are responsible for the induced in situ infiltration of mononuclear cells that markedly resembled natural killer (NK) cells in their cytochemical characteristics and surface markers.
Antitumor activity of the DNA fraction from Mycobacterium bovis BCG. II. Effects on various syngeneic mouse tumors.
TLDR
MY-1 was equally effective in mice with or without presensitization with BCG, whereas BCG was much more effective in BCG-sensitized mice, suggesting that a delayed-type hypersensitivity reaction elicited by BCG protein is not required for the antitumor activity of MY-1.
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