Journal article

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

Catarina F Almeida, Srinivasan Sundararaj, Jerome Le Nours, T Praveena, Benjamin Cao, Satvika Burugupalli, Dylan GM Smith, Onisha Patel, Manfred Brigl, Daniel G Pellicci, Spencer J Williams, Adam P Uldrich, Dale I Godfrey, Jamie Rossjohn

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

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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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by Australian Research Council (ARC)


Awarded by Fundacao para a Ciencia e a Tecnologia (FCT)


Awarded by ARC


Awarded by NHMRC


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.