Identification of an Optimal TLR8 Ligand by Alternating the Position of 2'-O-Ribose Methylation.
Int J Mol Sci
; 23(19)2022 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-36232437
ABSTRACT
Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2'-O-ribose (2'-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2'-O-methylation is crucial for its function. To this end, we designed different 2'-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2'-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2'-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2'-O-methylated RNA derivatives as optimal TLR8 ligands.
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Base de dados:
MEDLINE
Assunto principal:
Receptor 7 Toll-Like
/
Receptor 8 Toll-Like
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article