DNA As an Adjuvant

DNA is a complex macromolecule with immunological properties that depend on base sequence. Although mammalian DNA is immunologically inert, DNA from bacteria has potent immunostimulatory properties that result from short sequence motifs called CpG motifs or immunostimulatory sequences (ISS). These motifs, which have the general structure of two 5′ purines, an unmethylated CpG motif, and two 3′ pyrimidines, occur much more commonly in bacterial DNA than mammalian DNA because of two main factors: CpG suppression and the frequent methylation of cytosine in this position in mammalian DNA (1 ). As a result, bacterial DNA displays (in code-like fashion) sequences emblematic of foreignness. This code allows DNA to function as a danger signal in the induction of innate immunity (2 ).