Self-stabilized CpG DNAs optimally activate human B cells and plasmacytoid dendritic cells.
We recently showed that 5'-terminal secondary structures in CpG DNA affect activity significantly more than those at the 3'-end [Biochem. Biophys. Res. Commun. 306 (2003) 948]. The need for an accessible 5'-end of CpG DNA for activity suggested that the receptor reads the DNA sequence from this end. In continuation of these studies, we have designed immunomodulatory oligonucleotides (IMOs), consisting of a nine-mer stimulatory domain, containing a CpG motif and a hairpin-loop structure at the 3'-end, referred to as self-stabilized CpG DNAs. We studied the ability of self-stabilized CpG DNAs to stimulate human B-cell proliferation and interferon-alpha (IFN-alpha) secretion in plasmacytoid dendritic cell (pDC) culture assays. Self-stabilized CpG DNAs activated human B cells and induced plasmacytoid dendritic cells to secrete high levels of IFN-alpha. While both stimulatory and secondary structures in CpG DNAs were required for pDC activation, CpG motifs were sufficient to activate B cells. Interestingly, CpG motifs were not required for activity in the hairpin duplex region. Further modifications of the hairpin duplex region with a mixture of oligodeoxynucleotides and oligo-2'-O-methylribonucleotides in a heteroduplex formation permitted activation of both human B cells and pDCs.
Cong
Yan-Ping
YP
Hybridon, Inc., 345 Vassar Street,Cambridge, MA 02139, USA.
Song
Sam S
SS
Bhagat
Lakshmi
L
Pandey
Rajendra K
RK
Yu
Dong
D
Kandimalla
Ekambar R
ER
Agrawal
Sudhir
S
D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*
D004247:DNA