Premium
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
Author(s) -
Gray Reginald C.,
Kuchtey John,
Harding Clifford V.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1006606
Subject(s) - cpg oligodeoxynucleotide , cpg site , tlr9 , cross presentation , biology , mhc class i , antigen presentation , antigen , mhc class ii , microbiology and biotechnology , immunology , major histocompatibility complex , immune system , t cell , dna methylation , biochemistry , gene expression , gene
Deoxycytidyl‐deoxyguanosine [(CpG) 3 ] oligodeoxynucleotides (ODNs) signal through TLR9 to induce type‐I IFN (IFN‐αβ) and IFN‐αβ‐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‐αβ‐dependent MHC‐I antigen cross‐presentation by myeloid DCs despite greatly differing for induction of IFN‐αβ (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‐α. CpG‐B ODNs were slightly more potent than CpG‐A or CpG‐C ODNs for induction of low levels of IFN‐αβ but less efficacious at high concentrations than CpG‐A or CpG‐C ODNs. Low levels of IFN‐αβ 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‐αβ. High sensitivity to IFN‐αβ 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‐αβ and may avoid unnecessarily high induction of IFN‐αβ.