Journal article

alpha-Glucuronosyl and alpha-glucosyl diacylglycerides, natural killer T cell-activating lipids from bacteria and fungi

Satvika Burugupalli, Catarina F Almeida, Dylan GM Smith, Sayali Shah, Onisha Patel, Jamie Rossjohn, Adam P Uldrich, Dale I Godfrey, Spencer J Williams

CHEMICAL SCIENCE | ROYAL SOC CHEMISTRY | Published : 2020

Abstract

Natural killer T cells express T cell receptors (TCRs) that recognize glycolipid antigens in association with the antigen-presenting molecule CD1d. Here, we report the concise chemical synthesis of a range of saturated and unsaturated α-glucosyl and α-glucuronosyl diacylglycerides of bacterial and fungal origins from allyl α-glucoside with Jacobsen kinetic resolution as a key step. These glycolipids are recognized by a classical type I NKT TCR that uses an invariant Vα14-Jα18 TCR α-chain, but also by an atypical NKT TCR that uses a different TCR α-chain (Vα10-Jα50). In both cases, recognition is sensitive to the lipid fine structure, and includes recognition of glycosyl diacylglycerides bear..

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Grants

Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by ARC Future Fellowship


Awarded by NHMRC Senior Principal Research Fellowships


Funding Acknowledgements

This work was supported by grants from the Australian Research Council (ARC) (DP160100597; CE140100011) and the National Health and Medical Research Council of Australia (NHMRC) ( 1113293 & 1016629). APU was supported by an ARC Future Fellowship (FT140100278); JR is supported by an Australian ARC Laureate Fellowship; DIG is supported by an NHMRC Senior Principal Research Fellowships (1117766); and SJW was supported by an ARC Future Fellowship (FT130100103).