Published online before print January 16, 2007

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(Journal of Leukocyte Biology. 2007;81:1075-1085.)
© 2007 by Society for Leukocyte Biology

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

Reginald C. Gray^*,, John Kuchtey^*,1 and Clifford V. Harding^*,,,2

^* Departments of Pathology and
Pharmacology and
Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio, USA

² Correspondence: Department of Pathology, WRB 5534, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-7288, USA. E-mail: cvh3{at}cwru.edu

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

Key Words: CpG oligodeoxynucleotides • antigen presentation • Toll-like receptor 9 • dendritic cells • type I interferon

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