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dc.contributor.authorBurugupalli, S
dc.contributor.authorAlmeida, CF
dc.contributor.authorSmith, DGM
dc.contributor.authorShah, S
dc.contributor.authorPatel, O
dc.contributor.authorRossjohn, J
dc.contributor.authorUldrich, AP
dc.contributor.authorGodfrey, DI
dc.contributor.authorWilliams, SJ
dc.date.accessioned2020-11-27T00:00:41Z
dc.date.available2020-11-27T00:00:41Z
dc.date.issued2020-02-28
dc.identifierpii: c9sc05248h
dc.identifier.citationBurugupalli, S., Almeida, C. F., Smith, D. G. M., Shah, S., Patel, O., Rossjohn, J., Uldrich, A. P., Godfrey, D. I. & Williams, S. J. (2020). alpha-Glucuronosyl and alpha-glucosyl diacylglycerides, natural killer T cell-activating lipids from bacteria and fungi. CHEMICAL SCIENCE, 11 (8), pp.2161-2168. https://doi.org/10.1039/c9sc05248h.
dc.identifier.issn2041-6520
dc.identifier.urihttp://hdl.handle.net/11343/252314
dc.description.abstractNatural 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 bearing branched (R- and S-tuberculostearic acid) and unsaturated (oleic and vaccenic) acids. The TCR footprints on CD1d loaded with a mycobacterial α-glucuronosyl diacylglyceride were assessed using mutant CD1d molecules and, while similar to that for α-GalCer recognition by a type I NKT TCR, were more sensitive to mutations when α-glucuronosyl diacylglyceride was the antigen. In summary, we provide an efficient approach for synthesis of a broad class of bacterial and fungal α-glycosyl diacylglyceride antigens and demonstrate that they can be recognised by TCRs derived from type I and atypical NKT cells.
dc.languageEnglish
dc.publisherROYAL SOC CHEMISTRY
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titlealpha-Glucuronosyl and alpha-glucosyl diacylglycerides, natural killer T cell-activating lipids from bacteria and fungi
dc.typeJournal Article
dc.identifier.doi10.1039/c9sc05248h
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentSchool of Chemistry
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleChemical Science
melbourne.source.volume11
melbourne.source.issue8
melbourne.source.pages2161-2168
melbourne.identifier.nhmrc1016629
melbourne.identifier.nhmrc1013667
melbourne.identifier.nhmrc1113293
melbourne.identifier.nhmrc1117766
melbourne.identifier.arcFT130100103
melbourne.identifier.arcDP160100597
melbourne.identifier.arcFT140100278
dc.rights.licenseCC BY-NC
melbourne.elementsid1431873
melbourne.contributor.authorWilliams, Spencer
melbourne.contributor.authorGodfrey, Dale
melbourne.contributor.authorRossjohn, Jamie
melbourne.contributor.authorUldrich, Adam
melbourne.contributor.authorPatel, Onisha
melbourne.contributor.authorDos Santos Sa E Almeida, Catarina
melbourne.contributor.authorShah, Sayali
melbourne.contributor.authorBurugupalli, Satvika
dc.identifier.eissn2041-6539
melbourne.identifier.fundernameidNHMRC, 1016629
melbourne.identifier.fundernameidNHMRC, 1013667
melbourne.identifier.fundernameidNHMRC, 1113293
melbourne.identifier.fundernameidNHMRC, 1117766
melbourne.identifier.fundernameidAustralian Research Council, FT140100278
melbourne.identifier.fundernameidAUST RESEARCH COUNCIL, FT130100103
melbourne.identifier.fundernameidAUST RESEARCH COUNCIL, DP160100597
melbourne.accessrightsOpen Access


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