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.
From: Department of Pathology, Center for AIDS Research, WRB 5534, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-7288, USA.
Journal of leukocyte biology
- Publish Date: Apr 2007
- ISSN: 0741-5400
- Volume: 81
- Issue: 4
- Pages: 1075-85
- Medium: Print
- Language: English
- Citation (JAMA): Gray Reginald C, Kuchtey John, Harding Clifford V, et al. 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.. J. Leukoc. Biol. Apr 2007;81:1075-85
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.
Mesh Headings (Keywords): Animals, Antigen Presentation, Cells, Cultured, CpG Islands, Cross-Priming, Dendritic Cells, Histocompatibility Antigens Class I, Interferon-alpha, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Oligodeoxyribonucleotides, Receptor, Interferon alpha-beta, Signal Transduction, Toll-Like Receptors
Check for Full Text / PubMed Unique Identifier (PMID): 17227820
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