ODN 2088 - TLR9 Antagonist

TLR9 Antagonist - Inhibitory ODN, preference towards mouse

Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG oligonucleotide (ODN) sequences that distinguish microbial DNA from mammalian DNA.

Studies suggest the existence of DNA sequences that can neutralize the stimulatory effect of CpG ODNs [1].

These sequences are characterized by three consecutive Gs downstream of a C or A, addition of a fourth G (G-tetrads) increases the inhibitory capability.

The most potent inhibitory sequences are (TTAGGG)4 found in mammalian telomeres [2] and ODN 2088 which derives from a stimulatory ODN by replacement of 3 bases [3].

Inhibitory ODNs act by disrupting the colocalization of CpG ODNs with TLR9 in endosomal vesicles without affecting cellular binding and uptake.

References:

1. Krieg AM. et al., 1998. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc Natl Acad Sci USA. 95(21): 12631-6.
2. Gursel I. et al., 2003. Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. J Immunol. 171(3):1393-400.
3. Stunz LL. et al., 2002. Inhibitory oligodinucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. Eur J Immunol. 32(5): 1212-22.