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Potent Th2 Cytokine Bias of Natural Killer T Cell by CD1d Glycolipid Ligands: Anchoring Effect of Polar Groups in the Lipid Component
Author(s) -
Inuki Shinsuke,
Kashiwabara Emi,
Hirata Natsumi,
Kishi Junichiro,
Nabika Etsuko,
Fujimoto Yukari
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201802983
Subject(s) - cd1d , glycolipid , chemistry , biasing , ligand (biochemistry) , cytokine , stereochemistry , affinities , receptor , biochemistry , biology , natural killer t cell , immunology , cytotoxic t cell , in vitro , physics , quantum mechanics , voltage
Th2‐biasing CD1d ligands are attractive potential candidates for adjuvants and therapeutic drugs. However, the number of potent ligands is limited, and their biasing mechanism remain unclear. Herein, a series of novel Th2‐biasing CD1d glycolipid ligands, based on modification of their lipid part, have been identified. These have shown high binding affinities and efficient Th2 cytokine production. Importantly, the truncated acyl chain containing variants still retain their binding affinities and agonistic activities, which can be associated with an “anchoring effect,” that is, formation of a buried hydrogen bond between a polar group on the acyl chain and the CD1d lipid‐binding pocket. The analysis indicated that the appearance rates of ligand–CD1d complexes on the cell surface were involved in Th2‐biasing responses. The designed ligands, having the anchor in the shorter lipid part, are one of the most potent Th2‐biasing ligands among the known ligands.