CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis

CA James; KKQ Yu; M Gilleron; J Prandi; VR Yedulla; ZZ Moleda; E Diamanti; M Khan; VK Aggarwal; JF Reijneveld; P Reinink; S Lenz; RO Emerson; TJ Scriba; MNT Souter; DI Godfrey; DG Pellicci; DB Moody; AJ Minnaard; C Seshadri; I Van Rhijn

Journal article

CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis

CA James, KKQ Yu, M Gilleron, J Prandi, VR Yedulla, ZZ Moleda, E Diamanti, M Khan, VK Aggarwal, JF Reijneveld, P Reinink, S Lenz, RO Emerson, TJ Scriba, MNT Souter, DI Godfrey, DG Pellicci, DB Moody, AJ Minnaard, C Seshadri Show all

Cell Chemical Biology | CELL PRESS | Published : 2018

DOI: 10.1016/j.chembiol.2018.01.006

Abstract

Mycobacterial cell wall lipids bind the conserved CD1 family of antigen-presenting molecules and activate T cells via their T cell receptors (TCRs). Sulfoglycolipids (SGLs) are uniquely synthesized by Mycobacterium tuberculosis, but tools to study SGL-specific T cells in humans are lacking. We designed a novel hybrid synthesis of a naturally occurring SGL, generated CD1b tetramers loaded with natural or synthetic SGL analogs, and studied the molecular requirements for TCR binding and T cell activation. Two T cell lines derived using natural SGLs are activated by synthetic analogs independently of lipid chain length and hydroxylation, but differentially by saturation status. By contrast, two ..

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University of Melbourne Researchers

Michael Souter Author

Dale Godfrey Author

Daniel Pellicci Author

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Grants

Awarded by Doris Duke Charitable Foundation

Funding Acknowledgements

The work was supported by the University of Washington Department of Medicine and Royalty Research Fund (to C.S.), U.S. NIH (R01 AI-125189 to C.S.), and Doris Duke Charitable Foundation Clinical Scientist Development Award (to C.S.). A Bill and Melinda Gates Foundation Vaccine Accelerator Award to D.B.M. The National Health and Medical Research Council of Australia (NHMRC 1113293) and the Australian Research Council (ARC; CE140100011) to D.I.G. D.I.G. is also supported by NHMRC Senior Principal Research Fellowship (1117766). C.A.J. was supported by a Molecular Medicine Training grant (T32 GM095421 07). We thank Prof. C. Schneider, University of Leipzig, for a donation of phthioceranic acid. R.O.E. has full-time employment and equity ownership at Adaptive Biotechnologies Corporation. A.J.M. and I.V.R. were supported by Nederlands wetenschappelijk onderzoek (NWO) CW (Toppunt 15.002) and ALW (824.02.002), respectively.