The influence of base sequence on the immunostimulatory properties of DNA

DNA is a complex macromolecule whose immunological properties vary with bas e sequences. As shown with synthetic oligonucleotides, potent immune stimul ation results from six base motifs called CpG motifs or immunostimulatory s equences (ISS). These sequences center on an unmethylated CpG dinucleotide and occur much more commonly in bacterial DNA than mammalian DNA. As such, CpG motifs may function as a danger signal to stimulate B cell activation a nd cytokine production. In addition to CpG motifs, runs of deoxyguanosine ( dG) residues in DNA can induce B cell activation and promote macrophage cyt okine expression by adjacent CpG motifs, The array of these sequences may d etermine the overall immune activity of a DNA molecule and affect such proc esses as host defense against infection as well as the use of plasmids and synthetic oligonucleotides to treat disease.