On antigen presenting cells, lipid antigens, including glycolipids such as α-GalCer are recognized by CD1d, which is a non-polymorphic MHC class I-like molecule. Complexes of glycolipid ligands and CD1d are recognized by T cell receptors (TCR) on NKT cells and induce the secretion of various cytokines, such as helper-T (Th)1 and Th2 cytokines. We have synthesized some series of glycolipids, including glycerol- and ceramide-type compounds, and investigated the modulation of their cytokine-biasing responses. Although Th2-biasing CD1d ligands are attractive potential candidates for adjuvants and therapeutic drugs for autoimmune diseases, only a limited number of potent ligands have been reported. We have recently identified a series of novel Th2-biasing CD1d glycolipid ligands that have modification at their lipid part of α-GalCer structure. The modifications lead to high binding affinities and efficient Th2 cytokine production. The appearance rates of ligand-CD1d complexes on the cell surface were also involved in Th2-biasing responses. A covalent α-GalCer derivative was also developed as potent CD1d ligands, which showed Th2-biasing response. We here demonstrate the importance of lipid binding affinity of glycolipids to the receptor proteins in the lipid antigen presentation, for the modulation of cytokine-biasing responses.

Immunomodulatory glycolipids: Synthesis and modulation of cytokine-biasing responses

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.