Immunostimulatory oligodeoxynucleotide requires a specific secondary structure
2010
Shimosato, T., Shinshu Univ., Minamiminowa, Nagano (Japan). Faculty of Agriculture
The molecular mechanism by which immunostimulatory sequences of oligodeoxynucleotides (ISS-ODNs) activate immune cells remains unclear. There is also no information on the relationship between the secondary structure and immunostimulation of ISS-ODNs. Therefore I focused on the role of the secondary structure, particularly the number of bases and the presence of consecutive T's (5'-TTTT-3') in the loop on immunostimulatory activity. I finally found that a six-base loop is optimal for immunostimulatory activity and the strong immunostimulatory ODNs require a 5'-C...G-3' self-stabilized stem structure. These structures may be important for the induction of the strong immunostimulation not only in non-CpG ODNs but also in CpG ODNs. These structures may be needed for the induction of a Th-1-type response via TLR9 by non-CpG ODNs. Although further study on the relationship between the immunostimulatory ODNs and the ODN binding pocket of TLR9 is needed to elucidate the molecular mechanism of ODN recognition, the current study emphasized an important role of immunostimulation by ODNs.
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