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Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing
unmethylated CpG motifs stimulate a strong innate immune response. This
stimulation can be abrogated by either removing the CpG DNA or adding
inhibitory/suppressive motifs. Suppression is dominant over stimulation
and is specific for CpG-induced immune responses (having no effect on
LPS- or Con A-induced activation). Individual cells noncompetitively
internalize both stimulatory and suppressive ODN. Studies using ODN
composed of both stimulatory and suppressive motifs indicate that
sequence recognition proceeds in a 5'
3' direction, and that a 5'
motif can block recognition of immediately 3' sequences. These findings
contribute to our understanding of the immunomodulatory activity of
DNA-based products and the rules that govern immune recognition of
stimulatory and suppressive motifs.
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