Oligonucleotide Sequences Required for Natural Killer Cell Activation

  title={Oligonucleotide Sequences Required for Natural Killer Cell Activation},
  author={Etsuro Kuramoto and Osamu Yano and Y Kimura and Makoto Baba and Tadashi Makino and Saburo Yamamoto and Toshiko Yamamoto and Tetsuro Kataoka and Tohru Tokunaga},
  journal={Japanese Journal of Cancer Research : Gann},
  pages={1128 - 1131}
Based on the previous finding that certain 30‐mer single‐stranded oligodeoxyribonucleotides (oligonucleotides) having particular 6‐mer palindromic sequences could induce interferon‐alpha and ‐gamma, and enhance natural killer activity, the present study was carried out to clarify the entire relationship between the activity and the sequence of 30‐mer oligonucleotides. The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5… 
Ability of oligonucleotides with certain palindromes to induce interferon production and augment natural killer cell activity is associated with their base length.
It is indicated that the immunostimulatory activity of oligonucleotides with certain palindromic sequences requires an oligon nucleotide at least 18 bases long.
Binding of oligoguanylate to scavenger receptors is required for oligonucleotides to augment NK cell activity and induce IFN.
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.
Hexamer palindromic oligonucleotides with 5'-CG-3' motif(s) induce production of interferon.
The results strongly suggest that the minimal essential structure required for IFN induction is the hexamer palindromic sequence with CG motif(s), and that oligonucleotides with NACGTN and NTCGAN sequences exhibited the strongest activity.
Lipofection of Synthetic Oligodeoxyribonucleotide Having a Palindromic Sequence of AACGTT to Murine Splenocytes Enhances Interferon Production and Natural Killer Activity
The results strongly suggest that the prerequisite for IFN production is not the binding of AAC‐22 to the cell surface receptors, but its penetration into the spleen cells.
Characterization and modulation of immune stimulation by modified oligonucleotides.
One of the most potent ODNs was shown to activate NK and B lymphocytes when administered in vivo, and it was found that phosphorothioate backbones were, in general, less stimulatory than phosphodiester backbones.
Novel chimeric immunomodulatory compounds containing short CpG oligodeoxyribonucleotides have differential activities in human cells.
CICs could be 'programmed' for IFN-alpha production or B cell activation as independent variables, and identification of the optimal motifs, spacers and structures for different biological properties allows for the assembly of CICs exhibiting a defined set of activities tailored for specific clinical applications.
Historical Perspectives
The response of higher animals against immunostimulatory DNA must be the most primitive but important mechanism for self-nonself discrimination against foreign DNA.
Immunostimulatory DNA sequences : an overview.
There have now been several reports that bacterial DNA or synthetic oligodeoxyribo-nucleotides containing bacterially derived sequences, stimulate the immune systems of mice and humans to first mount innate, and then antigen-specific (when foreign antigen is present), Th(1)-type responses.


Synthetic Oligonucleotides with Particular Base Sequences from the cDNA Encoding Proteins of Mycobacterium bovis BCG Induce Interferons and Activate Natural Killer Cells
It is suggested that certain palindrome sequences, like GACGTC, GGCGCC and TGCGCA, are essential for 30‐mer oligonucleotides, like BCG‐A4a, to induce IFNs.
Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity.
The results strongly suggest that the presence of the unique palindromic sequences, such as GACGTC, AGCGCT, and AACGTT, but not ACCGGT, is essential for the immunostimulatory activity of oligonucleotides.
Antitumor Activity of Synthetic Oligonucleotides with Sequences from cDNA Encoding Proteins of Mycobacterium bovis BCG
Results suggested that palindromic structure is essential for the antitumor activity of the synthetic oligonucleotides.
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
Selection of single-stranded DNA molecules that bind and inhibit human thrombin
The isolation of single-stranded DNA aptamers to the protease thrombin of the blood coagulation cascade is described and binding affinities in the range 25–200 nM are reported.
In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG.
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.
DNA from Bacteria, but Not from Vertebrates, Induces Interferons, Activates Natural Killer Cells and Inhibits Tumor Growth
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.
Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA.
These studies provide further evidence that DNA are not uniform in their immunologic activities likely because of their content of nonconserved structural determinants.
Stabilities of nearest‐neighbor doublets in double‐helical DNA determined by fitting calculated melting profiles to observed profiles
Melting profiles were calculated for restriction fragments of ϕX174 and fd phage DNAs and compared with experimental profiles. The algorithm of Fixman and Freire was slightly modified so that a
Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.
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.