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Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs
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Date
2001-02-15
Author
Verthelyi, D
Ishii, KJ
Gürsel, Mayda
Takeshita, F
Klinman, DM
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
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Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN, One cluster ("D") preferentially stimulates IFN-gamma production by NK cells, whereas the other ("K") stimulates cell proliferation and the production of IL-6 and IgM by monocytes and B cells. The distinct immunostimulatory properties of K and D ODN can improve the design of CpG-based products to achieve specific: therapeutic goals.
Subject Keywords
Immunology
URI
https://hdl.handle.net/11511/41573
Journal
JOURNAL OF IMMUNOLOGY
DOI
https://doi.org/10.4049/jimmunol.166.4.2372
Collections
Department of Biology, Article
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Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates t...
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Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells
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Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...
Effect of suppressive DNA on CpG-induced immune activation.
Yamada, H; Gursel, I; Takeshita, F; Conover, J; Ishii, KJ; Gürsel, Mayda; Takeshita, S; Klinman, DM (The American Association of Immunologists, 2002-11-15)
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 stimula...
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D. Verthelyi, K. Ishii, M. Gürsel, F. Takeshita, and D. Klinman, “Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs,”
JOURNAL OF IMMUNOLOGY
, pp. 2372–2377, 2001, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41573.