Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs

Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides tri gger a strong innate immune response in vertebrates. CpG ODN show promise a s vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of mot ifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurall y distinct "clusters" of immunostimulatory CpG ODN, One cluster ("D") prefe rentially stimulates IFN-gamma production by NK cells, whereas the other (" K") stimulates cell proliferation and the production of IL-6 and IgM by mon ocytes and B cells. The distinct immunostimulatory properties of K and D OD N can improve the design of CpG-based products to achieve specific: therape utic goals.