The NKT cell TCR repertoire can accommodate structural modifications to the lipid and orientation of the terminal carbohydrate of iGb3

G Cameron; JMH Cheng; DI Godfrey; MSM Timmer; BL Stocker; EM Dangerfield

Journal article

The NKT cell TCR repertoire can accommodate structural modifications to the lipid and orientation of the terminal carbohydrate of iGb3

G Cameron, JMH Cheng, DI Godfrey, MSM Timmer, BL Stocker, EM Dangerfield

Rsc Advances | ROYAL SOC CHEMISTRY | Published : 2022

DOI: 10.1039/d2ra02373c

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Abstract

Isoglobotrihexosylceramide (iGb3) is a known NKT cell agonist, however the specific interactions required to trigger NKT cell TCR activation in response to this mammalian glycolipid are not fully understood. Here we report the synthesis of 1,3-β-Gal-LacCer (βG-iGb3) that displays a β-linked terminal sugar. βG-iGb3 activated NKT cells to a similar extent as iGb3 with a terminal α-linkage, indicating that the conformation of the terminal sugar residue of iGb3 is not essential to facilitate NKT cell TCR recognition. In addition, the immunological activity of four recently described iGb3 analogues with modifications to their terminal sugar or lipid backbone were also investigated. These iGb3 ana..

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University of Melbourne Researchers

Garth Cameron Author

Dale Godfrey Author

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Awarded by Australian Research Council

Funding Acknowledgements

The authors would like to thank The Health Research Council New Zealand (Hercus Fellowship, B. L. S., 2013/33) and the National Health and Medical Research Council of Australia (NHMRC): 1113293, 1140126, 1117766, 2008913 and Australian Research Council (CE140100011) to D. I. G. for funding. The graphical abstract was created with BioRender.com (<URI>https://www.BioRender.com</URI>).