MEDI 106 |
| Oligodeoxynucleotides (ODN) containing natural CpG or synthetic stimulatory motifs and form secondary structures act as agonistsofTLR9 and induce high levels of IFN-alpha in human cell-based assays. Our previous studies showed that synthetic agonists of TLR9 with palindromic sequences (4) and hairpin ODN sequences (1) form secondary structures and induce potent immune responses in mouse and human cell-based assays. ODN with palindromic sequences that allow formation of overlapping duplex or hairpin structures have been reported by others as class C CpG ODN [5'-TCGTCGTTTTCGGCGCGCGCCG-3'(2), 5'-TCGTCGAACGTTCGAGATGAT-3' (3)]. In the present study we have examined the ability of the four types of sequences (1-4) to form intra- and inter-molecular secondary structures by thermal melting studies and correlated their immune responses in cell-based assays and in vivo in mice. Both intra- (A) and inter-molecular (B and C) secondary structure forming ODN induced potent immune responses in mouse and human cell-based assays. Surprisingly ODN which form intra-molecular structures (A) did not induce cytokines in vivo in mice. ODN that form inter-molecular structures B and C induced cytokine secretion in mice. These results suggest that ODNs which form intra-molecular structures (A), such as 1 and 2, may not be appropriate candidates for TLR9 mediated immune responses.
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Medicinal Chemistry |
