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

S Burugupalli; CF Almeida; DGM Smith; S Shah; O Patel; J Rossjohn; AP Uldrich; DI Godfrey; SJ Williams

Journal article

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

S Burugupalli, CF Almeida, DGM Smith, S Shah, O Patel, J Rossjohn, AP Uldrich, DI Godfrey, SJ Williams

Chemical Science | ROYAL SOC CHEMISTRY | Published : 2020

DOI: 10.1039/c9sc05248h

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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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University of Melbourne Researchers

Satvika Burugupalli Author

Catarina Dos Santos Sa E Almeida Author

Onisha Patel Author

Jamie Rossjohn Author

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Grants

Awarded by National Health and Medical Research Council

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).