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

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

doi:10.1038/s41467-019-12941-9

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

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

Research output: Contribution to journal › Article › Research › peer-review

25 Citations (Scopus)

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 positioning of a sulfatide-reactive type II NKT TCR. Our data also suggest that diverse type II NKT TCRs directed against distinct microbial or mammalian lipid antigens adopt multiple recognition strategies on CD1d, thereby maximising the potential for type II NKT cells to detect different lipid antigens.

Original language	English
Article number	5242
Number of pages	14
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12941-9
Publication status	Published - 20 Nov 2019

Keywords

antimicrobial responses
lymphocytes
MHC
structural biology

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10.1038/s41467-019-12941-9

295209938-oaFinal published version, 2.55 MB

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Almeida, C. F., Sundararaj, S., Le Nours, J., Praveena, T., Cao, B., Burugupalli, S., Smith, D. G. M., Patel, O., Brigl, M., Pellicci, D. G., Williams, S. J., Uldrich, A. P., Godfrey, D. I., & Rossjohn, J. (2019). Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors. Nature Communications, 10(1), Article 5242. https://doi.org/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{\textquoteright}-pocket-docking mode that contrasts sharply with the previously determined A{\textquoteright}-roof positioning of a sulfatide-reactive type II NKT TCR. Our data also suggest that diverse type II NKT TCRs directed against distinct microbial or mammalian lipid antigens adopt multiple recognition strategies on CD1d, thereby maximising the potential for type II NKT cells to detect different lipid antigens.",

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

Abstract

Keywords

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ARC Centre of Excellence in Advanced Molecular Imaging

Australian Synchrotron

Macromolecular Crystallisation Facility

Cite this

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

Abstract

Keywords

Access to Document

Other files and links

Projects

ARC Centre of Excellence in Advanced Molecular Imaging

Equipment

Australian Synchrotron

Macromolecular Crystallisation Facility

Cite this