EMAIL THIS PAGE TO A FRIEND

Journal of immunology (Baltimore, Md. : 1950)

Minimal sequence requirements for oligodeoxyribonucleotides activating human TLR9.


PMID 25780037

Abstract

Synthetic oligodeoxyribonucleotides (ODNs) containing CpG (unmethylated deoxycytidylyl-deoxyguanosine dinucleotide) motifs activate endosomal TLR9. The nucleotide sequence, length, and dimerization properties of ODNs modulate their activation of TLR9. We performed a systematic investigation of the sequence motifs of B-class and C-class phosphodiester ODNs to identify the sequence properties that govern TLR9 activation. ODNs shorter than 21 nt and with the adenosine adjacent to the cytidine-guanosine (CG) dinucleotide motif led to a significant loss of the propensity to activate TLR9. The distance between the stimulatory CpG motifs within the ODN fine-tunes the activation of B cells. The minimal ODNs that activate human TLR9 comprise 2 CG dinucleotides separated by 6-10 nt, where the first CpG motif is preceded by the 5'-thymidine and the elongated poly-thymidine tail at the 3' end of the ODN. The minimal sequence provides insight into the molecular mechanism of TLR9 ligand recognition. On the basis of sequence requirements, we conclude that two binding sites with different affinities for CG are formed in the human TLR9 dimer, with a very stringent binding site interacting with the 5' CpG motif.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

40725
1,3-Dimethyl-2-imidazolidinone, absolute, over molecular sieve (H2O ≤0.04%), ≥99.5% (GC)
C5H10N2O
40727
1,3-Dimethyl-2-imidazolidinone, ≥99.0% (GC)
C5H10N2O
193453
1,3-Dimethyl-2-imidazolidinone, reagent grade
C5H10N2O
32883
4-tert-Octylphenol monoethoxylate solution, 1 μg/mL in acetone, analytical standard
C16H26O2
32882
4-tert-Octylphenol monoethoxylate solution, 10 μg/mL in acetone, analytical standard
C16H26O2
RAB0520
Bovine IFNG / Interferon Gamma ELISA Kit, for serum, plasma and cell culture supernatants
RAB0581 Cotton Rat Ifng / Interferon Gamma ELISA Kit
03609
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
C10H16N2O8
03620
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
C10H16N2O8
03690
Ethylenediaminetetraacetic acid solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
C10H16N2O8
47072
Fluoride ion solution for ISE, 0.1 M F-, analytical standard (for ion-selective electrodes)
FNa
80373
Fluoride, certified anion standard solution, 1000 mg/kg F-, for ion chromatography, certified by BAM, according to ISO 17025
FNa
1295607
Glycerin, United States Pharmacopeia (USP) Reference Standard
C3H8O3
PHR1020
Glycerin, Pharmaceutical Secondary Standard; Certified Reference Material
C3H8O3
49779
Glycerol, tested according to Ph.Eur., anhydrous
C3H8O3
77067
Glycerol, analytical standard
C3H8O3
12146
Glycerol 3 M solution, 3 M
C3H8O3 · xH2O
RAB0224
Mouse IFN-γ ELISA Kit, for serum, plasma, cell culture supernatant
RAB0225
Mouse IFN-γ ELISA Kit, for cell and tissue lysates
RAB0227
Rat IFN-γ ELISA Kit, for serum, plasma and cell culture supernatant
71383
Sodium chloride, tested according to Ph.Eur.
ClNa
71387
Sodium chloride, certified reference material for titrimetry, certified by BAM, according to ISO 17025, ≥99.5%
ClNa
PHR1321
Sodium chloride, Pharmaceutical Secondary Standard; Certified Reference Material
ClNa
450022
Sodium fluoride, anhydrous, powder, 99.99% trace metals basis
FNa
PHR1408
Sodium Fluoride, certified reference material
FNa
67414
Sodium fluoride 0.5 M solution
FNa
71177
Sodium standard for AAS, ready-to-use, traceable to BAM, in H2O
ClNa