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CpG‐B ODNs induce low levels of IFNαβ and induce IFNαβ‐dependent MHC‐I cross‐presentation in DCs as effectively as CpG‐A, CpG‐C ODNs, and TLR agonists
Author(s) -
Gray Reginald Courtney,
Kuchtey John,
Harding Clifford V
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb71
Subject(s) - cpg oligodeoxynucleotide , tlr9 , tlr7 , cpg site , cross presentation , mhc class i , mhc class ii , chemistry , antigen presentation , microbiology and biotechnology , antigen , biology , immunology , major histocompatibility complex , toll like receptor , immune system , t cell , innate immune system , biochemistry , gene expression , gene , dna methylation
CpG oligodeoxynucleotides (ODNs) and single stranded RNAs (ssRNA) signal through TLR9 and TLR7, respectively, to induce type‐I IFN (IFNαβ) and IFNαβ‐dependent MHC‐I cross‐presentation of exogenous antigens (Ags) by dendritic cells (DCs). A puzzle was presented by our observation that three ODN classes, CpG‐A, CpG‐B and CpG‐C, and TLR7 agonists ssRNA40 and R837, had similar efficacy for induction of IFNαβ‐dependent‐MHC‐I Ag cross‐presentation by myeloid DCs (mDCs) despite greatly differing for induction of IFNαβ (CpG‐A > CpG‐C ~ TLR7 agonists >> CpG‐B). All ODN classes similarly enhanced plasmacytoid DC (pDC) presentation of exogenous MHC‐I‐restricted peptide, although pDCs did not cross‐process protein Ag. MHC‐I and the transporter for antigen presentation were induced by all ODN classes or IFNα. CpG‐B ODNs were slightly more potent than CpG‐A or CpG‐C ODNs for induction of low levels of IFNαβ, but less efficacious at high concentrations than CpG‐A or CpG‐C ODNs. Low levels of IFNαβ 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, CpG‐C ODNs or TLR7 agonists for induction of IFNαβ. High sensitivity to IFNαβ 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 IFNαβ and avoid unnecessarily high induction of IFNαβ.