title: Self-stabilized CpG DNAs optimally activate human B cells and plasmacytoid dendritic cells.
abstract: 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.
authors.affiliation: Hybridon, Inc., 345 Vassar Street,Cambridge, MA 02139, USA.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Cong
authors.forename: Sam S
authors.initials: SS
authors.lastname: Song
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Bhagat
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Pandey
authors.forename: Dong
authors.initials: D
authors.lastname: Yu
authors.forename: Ekambar R
authors.initials: ER
authors.lastname: Kandimalla
authors.forename: Sudhir
authors.initials: S
authors.lastname: Agrawal
mesh_terms: 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*
chemical_list: D004247:DNA