CpG-B ODNs potently induce low levels of IFN-αβ and induce IFN-αβ-dependent MHC-I cross-presentation in DCs as effectively as CpG-A and CpG-C ODNs

Deoxycytidyl-deoxyguanosine [(CpG)(3)] oligodcoxynuelcotides (ODNs) signal through TLR9 to induce type-I IFN (IFN-alpha beta) and IFN-alpha beta-dependent MHC-1 cross-presentation of exogenous antigens by dendritic cells (DCs). A puzzle was presented by our observation that three ODN classes, CpG-A, CpG-B, and CpG-C, had similar efficacy for induction of IFN-alpha beta-dependent MHC-1 antigen cross-presentation by myeloid DCs despite greatly differing for induction of IFN-alpha beta (CpG-A > CpG-C >> CpG-B). All ODN classes similarly enhanced plasmacytoid DC (pDC) presentation of exogenous MHC-I-restrieted peptide, although pDCs did not cross-process protein antigen. MHC-1 and the transporter for antigen presentation were induced by all ODN classes or IFN-alpha. CpG-B ODNs were slightly more potent than CpG-A or CpG-C ODNs for induction of low levels of IFN-alpha beta but less efficacious at high concentrations than CpG-A or CpG-C ODNs. Low levels of IFN-alpha beta induced by CpG-B ODNs sufficed for full induction of MHC-1 cross-presentation. Thus, CpG-B ODNs are slightly more potent but less efficacious than CpG-A and CpG-C ODNs for induction of IFN-alpha beta. High sensitivity to IFN-alpha beta allows CpG-B ODNs to be equally efficacious for induction of MHC-1 cross-presentation. CpG-B ODNs may be effective for inducing therapeutic responses that require low levels of IFN-alpha beta and may avoid unnecessarily high induction of IFN-alpha beta.