BINDING OF OLIGOGUANYLATE TO SCAVENGER RECEPTORS IS REQUIRED FOR OLIGONUCLEOTIDES TO AUGMENT NK CELL-ACTIVITY AND INDUCE IFN

Specific palindromic sequences in synthetic oligonucleotides are requi red to induce IFN and augment IFN-mediated natural killer activity. To study the mechanism of IFN induction by oligonucleotides containing p alindromic sequences, we investigated the possible target molecules of the oligonucleotides. Oligo-1, a 30mer single-stranded oligonucleotid e with oligoG sequences next to the active palindromic sequence (AACGT T), had more activity than oligonucleotides with oligoA, oligoC, or ol igoT sequences. The activity of oligo-1 was inhibited by a guanine hom o-oligomer (G30), dextran sulfate, and polyvinyl sulfate. Oligo-1 boun d to plastic-adherent mouse splenocytes, and the binding was inhibited by G30, dextran sulfate, and polyvinyl sulfate. Oligo-1 inhibited ace tyl-LDL binding to the scavenger receptor on mouse splenocytes. These findings suggest that the binding of an extrapalindromic sequence to t he scavenger receptor is required for the immunostimulatory activity o f oligo-1.