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Rational design of ...
Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells.
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Hartmann, Gunther (author)
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Battiany, Julia (author)
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Poeck, Hendrik (author)
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Wagner, Moritz (author)
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Kerkmann, Miren (author)
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- Lubenow, Norbert (author)
- Department of Transfusion Medicine, Greifswald University, Germany
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Rothenfusser, Simon (author)
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Endres, Stefan (author)
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(creator_code:org_t)
- Wiley, 2003
- 2003
- English.
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 33:6, s. 1633-41
- Related links:
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Two different types of CpG motif-containing oligonucleotides (CpG ODN) have been described: CpG-A with high induction of IFN-alpha in plasmacytoid dendritic cells; and CpG-B with little induction of IFN-alpha, but potent activation of B cells. In this study, we demonstrate that CpG-A fail to activate B cells unless plasmacytoid dendritic cells are present. We identified a new set of CpG ODN sequences which induces high levels of IFN-alpha in plasmacytoid dendritic cells but remains capable of directly activating B cells. These new CpG ODN (termed CpG-C) are more potent stimulants of B cells than CpG-B due to their ability of directly and indirectly (via plasmacytoid dendritic cells) activating B cells. The sequence of CpG-C combines structural elements of both CpG-A and CpG-B. The most potent sequence, M362, contains a 5'-end 'TCGTCG-motif' and a 'GTCGTT-motif', both of which are present in CpG-B (ODN 2006); a palindromic sequence characteristic for CpG-A (ODN 2216); but no poly G motif required for CpG-A. In conclusion, we defined the first CpG-containing sequences that potently activate both TLR9-expressing immune cell subsets in humans, the plasmacytoid dendritic cell and the B cell. CpG-C may allow for improved therapeutic immuno-modulation in vivo.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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