CpG oligodeoxynucleotide

Source: Wikipedia, the free encyclopedia.
Not to be confused with CpG site.
The different classes of ODN elicit different responses in pDC and B cells. Class A strongly stimulates pDC and the production of IFNα. Class B strongly stimulates B cells and antibody production. Class C moderately stimulates both cell types. Class P elicits a response similar to Class A while Class S competitively inhibits the response.
The different classes of ODN elicit different responses in pDC and B cells.

CpG oligodeoxynucleotides (or CpG ODN) are short single-stranded synthetic

dendritic cells (pDCs) in humans and other higher primates.[3]

History

Since 1893, it has been recognized that

Coley's toxin, a mixture of bacterial cell lysate, has immunostimulatory properties that could reduce the progression of some carcinomas,[4] but it was not until 1983 that Tokunaga et al. specifically identified bacterial DNA as the underlying component of the lysate that elicited the response.[5] Then, in 1995 Krieg et al. demonstrated that the CpG motif within bacterial DNA was responsible for the immunostimulatory effects and developed synthetic CpG ODN.[6] Since then, synthetic CpG ODN have been the focus of intense research due to the Type I pro-inflammatory response they elicit and their successful use as vaccine adjuvants.[citation needed
]

Structural features

Synthetic CpG ODN differ from microbial DNA in that they have a partially or completely

PBMCs). The five classes are Class A (Type D), Class B (Type K), Class C, and Class P.[9] It is important to note that during the discovery process, the "Classes" were not defined until much later when it became evident that ODN with certain characteristics elicited specific responses. Because of this, most ODN referred to in the literature use numbers (i.e., ODN 2006, ODN 2007, ODN 2216, ODN D35, ODN K3, etc.). The numbers are arbitrary and come from testing large numbers of ODN with slight variations in attempts to find the optimal sequence. In addition, some papers will give different names to previously described ODN, complicating the naming convention even more.[citation needed
]

Class A

One of the first Class A ODN, ODN 2216, was described in 2001 by Krug et al.[10] This class of ODN was distinctly different from the previously described Class B ODN (i.e., ODN 2006) in that it stimulated the production of large amounts of Type I interferons, the most important one being IFNα, and induced the maturation of plasmacytoid dendritic cells. Class A ODN are also strong activators of NK cells through indirect cytokine signaling.

Structural features defining Class A ODN:

  • The presences of a poly G sequence at the 5' end, the 3' end, or both
  • An internal palindrome sequence
  • GC dinucleotides contained within the internal palindrome
  • A partially PS-modified backbone

Class A ODN typically contain 7 to 10 PS-modified bases at one or both ends that resist degradation by nucleases and increase the longevity of the ODN. The above rules strictly define the class, but variability of the sequence within these "rules" is possible. It should also be noted that changes to the sequence will affect the magnitude of the response. For example, the internal palindrome sequence can be 4 to 8 base pairs in length and vary in the order of bases, however the pattern, 5'-Pu Pu CG Pu Py CG Py Py-3', was found to be the most active when compared to several other sequences. The poly G tail found at either end of the DNA strand can vary in length and even number (Type D only have a poly G sequence on the 3'end), but its presence is critical to the activity of the molecule.[citation needed]

Class B

Krieg et al. was the first to describe Class B ODN in 1995.[6] Class B ODN (i.e. ODN 2007) are strong stimulators of human B cell and monocyte maturation. They also stimulate the maturation of pDC but to a lesser extent than Class A ODN and very small amounts of IFNα.[citation needed]

Structural features defining Class B ODN:

  • One or more 6mer CpG motif 5'-Pu Py C G Py Pu-3'
  • A fully phosphorothioated (PS-modified) backbone
  • Generally 18 to 28 nucleotides in length

The strongest ODN in this class have three 6mer sequences.[11] B ODN have been studied extensively as therapeutic agents because of their ability to induce a strong humoral immune response, making them ideal as a vaccine adjuvant.

References

  1. PMID 9380720
    .
  2. PMID 12467249
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  3. PMID 12480254
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  4. PMID 1984929
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  5. PMID 6200641
    .
  6. ^
    S2CID 4261304
    .
  7. PMID 11972638
    .
  8. PMID 15184382
    .
  9. PMID 19211030
    .
  10. PMID 11449369
    .
  11. PMID 10640783
    .
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