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The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode.

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Li Y, Girardi E, Wang J, Yu ED, Painter GF, Kronenberg M, Zajonc DM
OpenAccess logo J Exp Med 207 2383-93 (2010)
Cited: 67 times
EuropePMC logo PMID: 20921281

Abstract

Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-α-dependent structural changes in the F' roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen α-galactosylceramide (α-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi α-galactosyl diacylglycerol-CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles α-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with α-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes.

Reviews - 3o9w mentioned but not cited (4)

  1. Recognition of CD1d-restricted antigens by natural killer T cells. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI. Nat Rev Immunol 12 845-857 (2012)
  2. Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells. Girardi E, Zajonc DM. Immunol Rev 250 167-179 (2012)
  3. NKT cell ligand recognition logic: molecular basis for a synaptic duet and transmission of inflammatory effectors. Joyce S, Girardi E, Zajonc DM. J Immunol 187 1081-1089 (2011)
  4. Molecular recognition of microbial lipid-based antigens by T cells. Gras S, Van Rhijn I, Shahine A, Le Nours J. Cell Mol Life Sci 75 1623-1639 (2018)

Articles - 3o9w mentioned but not cited (2)



Reviews citing this publication (25)

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  8. Recognition of Microbial Glycolipids by Natural Killer T Cells. Zajonc DM, Girardi E. Front Immunol 6 400 (2015)
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  22. Immune sensing of microbial glycolipids and related conjugates by T cells and the pattern recognition receptors MCL and Mincle. Smith DG, Williams SJ. Carbohydr Res 420 32-45 (2016)
  23. Structure-activity relationship studies of novel glycosphingolipids that stimulate natural killer T-cells. Tashiro T. Biosci Biotechnol Biochem 76 1055-1067 (2012)
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