Cells of the immune system are able to detect the presence of pathogens with an array of receptors that recognize pathogen-associated molecular patterns (PAMPs). Detection of PAMPs initiates various events, including the production of inflammatory signals and activation of antigen presenting cells, which promote the induction of adaptive immunity. Synthetic PAMPs, such as CpG oligonucleotides (ODNs), are commonly used as adjuvants to enhance immune responses in both experimental and clinical settings. Recently, DEC-205, a C-type lectin-like receptor found on various cells of the immune system, including dendritic cells, B cells and T cells, was discovered to be a receptor for CpG ODNs. Significantly, binding to DEC-205 appears to be important for optimal immune stimulation by CpG ODNs, as the ODN 1668 is markedly less stimulatory in the absence of DEC-205. We build upon these findings by further characterising the interaction between CpG ODNs and DEC-205, and how this impacts on the immunostimulatory function of CpG ODNs.
Not all ODNs bind to DEC-205 equally efficiently. To determine the molecular requirements for optimal DEC-205 binding, we compared the abilities of ODNs of varying lengths and sequences to bind DEC-205. The optimal binding sequence found in this way was then used to investigate the functional consequences of DEC-205 binding. DEC-205 binding by a previously poor-binding CpG ODN could be drastically improved by addition of the optimal binding sequence. Strikingly, the improved DEC-205 binding also improved the adjuvant activity of the ODN. More potent immune responses were induced when the modified ODN was used as an adjuvant compared with the original ODN. These results indicate that improved DEC-205 binding enhances the immunostimulatory effects of CpG ODNs, which can be used to design more effective adjuvants.