TLR9 agonists

Toll-like receptor 9 (TLR9) is critical for distinguishing foreign from mammalian DNA during the early innate immune response. The receptor is localized in the endosomal compartment and recognizes the unmethylated CpG-containing motifs of bacterial and viral DNA. Upon recognition, MYD88 (myeloid differentiation primary response 88) is recruited to the receptor and the TLR9 pathway is activated. The signaling cascade finally leads to the activation of the transcription factors NF-κB, AP-1, and/or IRF-7. Thus, the expression of pro-inflammatory cytokines and type I IFNs is triggered, which initiates the immune response.  

TLR9 is mainly expressed in antigen-presenting cells, such as B cells or dendritic cells (DCs), and activation of the pathway leads to the maturation of the respective cell. Besides its functions for detecting infections, TLR9 signaling appears to play a role in cancer, tissue damage, and several autoimmune diseases.  

Synthetic oligodesoxynucleotides (ODNs) containing CpG motifs (CpG ODNs) can mimic the immune stimulatory effect of naturally occurring ligands, functioning as TLR9 agonists. We provide high-quality CpG ODNs for activating immune cells and the respective controls. Control compounds for CpG ODNs share the sequence with their stimulatory counterparts but contain GpC dinucleotides instead of the CpG motifs. Thus, the CpG-specificity of the stimulatory effect can be shown, when using CpG ODNs and the respective controls. 

Overview of available TLR9 agonists

Based on the functional and structural characteristics, CpG ODNs are divided into different classes:  

  • A-class: contain 5' and/or 3' G-rich stretches and a central CpG-containing palindromic motif
  • B-class: consist of a fully phosphorothioated backbone with one or more CpG dinucleotides
  • C-class: consist of a fully phosphorothioated backbone witch a CpG-containing palindromic motif
  • P-class: contain two palindromic sequences

Choose between different TLR9 agonist based on their ODN class and functional characteristics: 

Table 1: Overview of available products of different ODN classes.
*Phosphorothioate backbone

ODN classProduct groupProductSequenceStructural characteristicsFunctional characteristics
A-classAgonistODN 2216dG*dG*dG-dG-dG-dA-dC-dG-dA-dT-dC-dG-dT-dC-dG*dG*dG*dG*dG*dGForm tertiary structures (G tetrads)Induce high levels of IFN-α but show low activation of B cell proliferation. 
Useful for pDC activation and IFN-α induction from human PBMCs and activation of IFN-signaling pathways. 
Control ODNODN 2216 Control (ODN 2243)dG*dG*dG-dG-dG-dA-dG-dC-dA-dT-dG-dC-dT-dC-dG*dG*dG*dG*dG*dG   
B-classAgonistsODN 1826 dT*dC*dC*dA*dT*dG*dA*dC*dG*dT*dT* dC*dC*dT*dG*dA*dC*dG*dT*dT  Activate B cells and TLR9-dependent NF-κB signaling but induce low expression of IFN-α. 
Utilized in B cell activation and IL-6 induction from human PBMCs and activation of NF-κB signaling pathways. 
ODN 2006dT*dC*dG*dT*dC*dG*dT*dT*dT*dT*dG*dT* dC*dG*dT*dT*dT*dT*dG*dT*dC*dG*dT*dT 
Control ODNsODN 1826 Control (ODN 2138)dT*dC*dC*dA*dT*dG*dA*dG*dC*dT*dT*dC* dC*dT*dG*dA*dG*dC*dT*dT   
ODN 1982dT*dC*dC*dA*dG*dG*dA*dC*dT*dT*dC*dT* dC*dT*dC*dA*dG*dG*dT*dT  
ODN 2006 Control (ODN 2137)dT*dG*dC*dT*dG*dC*dT*dT*dT*dT*dG*dT* dG*dC*dT*dT*dT*dT*dG*dT*dG*dC*dT*dT  
C-classAgonistODN 2395dT*dC*dG*dT*dC*dG*dT*dT*dT*dT*dC*dG* dG*dC*dG*dC*dG*dC*dG*dC*dC*dG Form dimeric structuresStrongly induce IFN-α production by pDCs as well as B cell stimulation.
Control ODNODN 2395  Control (ODN 5328)dT*dG*dC*dT*dG*dC*dT*dT*dT*dT*dC*dG* dG*dC*dG*dC*dG*dC*dG*dC*dC*dG  
P-classAgonistODN 21798dT*dC-dG*dT*dC-dG*dA*dC-dG*dA*dT* dC-dG*dG*dC*dG*dC-dG*dC*dG*dC*dC*dGForm multimeric structuresActivate both pDCs and B cells with higher efficiency than C-class agonists.
Control ODNODN 21798 Control (ODN 23098)dT*dG-dC*dT*dC-dG*dA*dC-dG*dA*dT*dC-dG*dG*dC*dG*dC-dG*dC*dG*dC*dC*dG   

Interested in getting a comprehensive package of different TLR9 ligands?

Have a look at our TLR9 Explorer. The kit comprises TLR9 agonists of all four ODN classes and their respective controls. It includes ODN 2216 (A-class), ODN 2006 (B-class), ODN 2395 (C-class), ODN 21798 (P-class), and the respective control ODNs (ODN 2243, ODN 2137, ODN 5328, and ODN 23098).

Specific efficiencies of different ODN classes

TLR9 ligands of the four ODN classes differ in their functional characteristics and thus in their efficiencies. To help you to choose the product that fist best to your needs, we have summarized the information in table 2. 

Table 2: Overview of the specific efficiencies of the four ODN classes.

IFN-α secretion / induction++++++++++++++
B cell stimulation+++++++++
IL-6 secretion / induction+++++++++

TLR ligand in MACS® GMP Quality

Looking to transition your experiment into clinical research? Our P-class TLR9 agonist is also available in MACS GMP Quality. See MACS GMP CpG-P.


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TLR9 agonists – Effective immune cell activation

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