An immunostimulatory composition comprising a 4-mer RNA motif provided as 5'-N1-U-U-G-U-N2-3', wherein N1 and N2 independently are RNA sequences 0-10 nucleotides long. The 4-mer motif is sufficient to confer new and altered immunostimulatory properties in new and existing oligonucleotides. Also provided are methods of stimulating an immune response comprising administering said immunostimulatory 4-mer motif composition.