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. 2021 Feb 23;12:590054. doi: 10.3389/fimmu.2021.590054

Table 4.

CpG classes: sequences, structure, interaction with Toll-like receptor 9 (TLR9), and response induced in immune cells.

CpG-ODN type Sequence example Structure Effect on Immune cells
A-class (D-type) GGTGCPuPy CG PuPyGCAGGGGGG Single CpG motif flanked by a palindromic sequence, plus a 3’ Poly-G end.
Mixed phosphodiester/phosphorothioate backbone.
• IFNγ production by NK cells (83)§
• Lytic activity by NK cells (128)§#
• Type 1 IFN production by pDC (85, 129, 130)§#
B-class (K-type) ATCGACTCTCGAGCGTTCTC Multiple CpG motifs. No palindromic sequences.
Phosphorothioate only backbone.
• IgM, IL-6 production by B cells and B cell proliferation (83, 131)§
• Type 1 IFN production by pDC (85)§
• pDC maturation (130)§
• Th1 response induction (85)§
• NK cells activation (85)§
• Production of TGF-β and IDO by pDC (84, 132)§#
• Tolerance induction by pDC (77, 84, 132)§#
C-class TCG T CG TT CG AA CG A CGTTGAT Multiple CpG motifs and one palindromic sequence.
Phosphorothioate only backbone
• IL-6 production by B cells (131, 133)§
• B cell activation and proliferation (134)§
• Type I IFN in pDC (130)§
• pDC maturation (130)§
P-class T CG T CG A CG AT-CG G CGCGCG C CG Multiple CpG motifs flanked and two palindromic sequences.
Phosphorothioate only backbone.
• Type I IFN by PBMCs (135)§
• Increased plasma levels of type 1 IFN and IL-6 in vivo (135)§

Pu, purine nucleotide; Py, pyrimidine nucleotide; Bold, CpG motifs; Underlined, palindrome sequences; PBMCs, peripheral blood mononuclear cells. #In mouse, §In human.