CpG motif

CpG stands for cytosine phosphate guanine dinucleotide in a particular sequence context. CpG motifs are responsible for proliferative effects of antisense oligonucleotides, particularly with respect to B-lymphocytes. Die optimal immune-stimulatory consensus sequence surrounding CpG is R1R2CGY1Y2, where R1 is a purine (mild preference for G), R2 is a purine or T (preference for A), and Y1 and Y2 are pyrimidines (preference for T). 

Krieg, A.M., CpG motifs in bacterial DNA and their immune effects, Annu. Rev Immunol, 20, 709, 2002. 

Balias, Z.K. et al., Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs, J Immunol, 167, 4878, 2001. 

Klinman DM, Yamshchikov G, Ishigatsubo Y (1997) Contribution of CpG motifs to the immuno-genicity of DNA vaccines. J. Immunol. 158 3635-3639. 

Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374 546-549. 

It has been demonstrated that the unmethylated CpG motifs in the DNA activate DCs through TLR9, but association with the cationic liposome is required for full activation of these cells. Because the liposomes alone do not generate a cytokine response, we can suppose there is a second receptor... 

The primary structure of DNA is a one-dimensional system similar to four-letter text and can be subjected to the simplest combinatory rules. The particular motifs can be combined with one or several other motifs in away similar to using building blocks. For instance, G-rich motif can be added to one or both ODN flanks. A certain sequence, e.g., a sequence containing unmethylated deoxyribodi-nucleotide CpG motifs that mimic prokaryotic DNA (I), can be placed between similar or different motifs, like GC-rich palindrome and/or G-rich motifs (Fig. I). Various motif combinations will yield a number of putative DNA sequence variants that can be used for further tests and selection of perspective ODN compounds (see Notes 1-4). 

Deoxy 2V methyl modification G-rich motifs have black background sequences containing unmethylated CpG motifs are shown with jjrey background (corresponding to drawing in Fig. 1)... 

Fig. 1. The three structural levels of DNA-based Immunomodulatory sequence (DIMS). G-rich motifs are shown in blacK, sequences containing unmethylated CpG motifs shown in grey (corresponding to the color of motif background in Table 1) thin grey/mes indicate hydrogen bonds formed by Watson-Crick nucleotide pairs (DNA secondary structure level) or by Floogsteen hydrogen bonding (DNA tertiary structure level).

Klinman DM, Barnhart KM, Conover J. CpG motifs as immune adjuvants. Vaccine 1999 17 19-25. 

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