title: CpG-B ODNs potently induce low levels of IFN-alphabeta and induce IFN-alphabeta-dependent MHC-I cross-presentation in DCs as effectively as CpG-A and CpG-C ODNs.
abstract: Deoxycytidyl-deoxyguanosine [(CpG)3] oligodeoxynucleotides (ODNs) signal through TLR9 to induce type-I IFN (IFN-alphabeta) and IFN-alphabeta-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-alphabeta-dependent MHC-I antigen cross-presentation by myeloid DCs despite greatly differing for induction of IFN-alphabeta (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-alpha. CpG-B ODNs were slightly more potent than CpG-A or CpG-C ODNs for induction of low levels of IFN-alphabeta but less efficacious at high concentrations than CpG-A or CpG-C ODNs. Low levels of IFN-alphabeta 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-alphabeta. High sensitivity to IFN-alphabeta 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-alphabeta and may avoid unnecessarily high induction of IFN-alphabeta.
authors.affiliation: Department of Pathology, Center for AIDS Research, WRB 5534, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-7288, USA.
authors.forename: Reginald C
authors.initials: RC
authors.lastname: Gray
authors.forename: John
authors.initials: J
authors.lastname: Kuchtey
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D018899:CpG Islands; D045142:Cross-Priming; D003713:Dendritic Cells / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000819:agonists
chemical_list: C408982:CPG-oligonucleotide; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors; D053633:Receptor, Interferon alpha-beta