Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors

CF Almeida; S Sundararaj; J Le Nours; T Praveena; B Cao; S Burugupalli; DGM Smith; O Patel; M Brigl; DG Pellicci; SJ Williams; AP Uldrich; DI Godfrey; J Rossjohn

Journal article

Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors

CF Almeida, S Sundararaj, J Le Nours, T Praveena, B Cao, S Burugupalli, DGM Smith, O Patel, M Brigl, DG Pellicci, SJ Williams, AP Uldrich, DI Godfrey, J Rossjohn

Nature Communications | NATURE PORTFOLIO | Published : 2019

DOI: 10.1038/s41467-019-12941-9

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Abstract

Type I and type II natural killer T (NKT) cells are restricted to the lipid antigen-presenting molecule CD1d. While we have an understanding of the antigen reactivity and function of type I NKT cells, our knowledge of type II NKT cells in health and disease remains unclear. Here we describe a population of type II NKT cells that recognise and respond to the microbial antigen, α-glucuronosyl-diacylglycerol (α-GlcADAG) presented by CD1d, but not the prototypical type I NKT cell agonist, α-galactosylceramide. Surprisingly, the crystal structure of a type II NKT TCR-CD1d-α-GlcADAG complex reveals a CD1d F’-pocket-docking mode that contrasts sharply with the previously determined A’-roof position..

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University of Melbourne Researchers

Catarina Dos Santos Sa E Almeida Author

Satvika Burugupalli Author

Onisha Patel Author

Daniel Pellicci Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

We thank Prof. Michael Brenner for the gift of key type II NKT cell reagents and Maria Sandoval and Christine Wang for technical assistance. We thank the staff at the Australian Synchrotron for assistance with data collection, the staff at the Monash Macromolecular crystallisation facility and the staff from the University of Melbourne flow cytometry facilities. This research was undertaken on the MX1 and MX2 beamlines at the Australian Synchrotron, part of ANSTO. This work was supported by a programme grant from the National Health and Medical Research Council of Australia (NHMRC) (1013667 and 1016629) and the Australian Research Council (ARC) (CE140100011 and DP160100597). C.F.A. was supported by a Fundacao para a Ciencia e a Tecnologia (FCT) (SFRH/BD/74906/2010); J.L.N. is supported by an ARC Future Fellowship (FT160100074); D.G.P. is supported by a CSL Centernary Fellowship; S.J.W is supported by an ARC Future Fellowship (FT130100103); A.P.U. is supported by an ARC Future Fellowship (FT140100278); D.I.G. is supported by NHMRC Senior Principal Research Fellowship (1117766); J.R. is supported by an Australian ARC Laureate Fellowship.