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Invariant natural killer T cells recognise lipid self antigen induced by microbial danger signals

Invariant natural killer T cells recognise lipid self antigen induced by microbial danger signals
Invariant natural killer T cells recognise lipid self antigen induced by microbial danger signals
Invariant natural killer T cells (iNKT cells) have a prominent role during infection and other inflammatory processes, and these cells can be activated through their T cell antigen receptors by microbial lipid antigens. However, increasing evidence shows that they are also activated in situations in which foreign lipid antigens would not be present, which suggests a role for lipid self antigen. We found that an abundant endogenous lipid, ?-D-glucopyranosylceramide (?-GlcCer), was a potent iNKT cell self antigen in mouse and human and that its activity depended on the composition of the N-acyl chain. Furthermore, ?-GlcCer accumulated during infection and in response to Toll-like receptor agonists, contributing to iNKT cell activation. Thus, we propose that recognition of ?-GlcCer by the invariant T cell antigen receptor translates innate danger signals into iNKT cell activation
1529-2908
Brennan, Patrick J.
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Tatituri, Raju V.V.
c821e237-49b7-40a0-a576-19d33c60cb83
Brigl, Manfred
e708e1fc-35dd-41c8-a2c6-e13583ea4493
Kim, Edy Y.
f57eabf2-a422-4be5-936e-bf224cebf11e
Tuli, Aamit
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Sanderson, Joseph P.
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Gadola, Stephan D.
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Hsu, Fong-Fu
d6827f7d-06c3-45b3-810b-5c859d0fa0e6
Besra, Gurdyal S.
b3523122-c452-4efc-b625-d80744586a47
Brenner, Michael B.
ec8181bd-a1b3-4f00-b2fb-8a7799a80797
Brennan, Patrick J.
a8f4fcc0-39ce-4827-b4e6-be5b3e372e26
Tatituri, Raju V.V.
c821e237-49b7-40a0-a576-19d33c60cb83
Brigl, Manfred
e708e1fc-35dd-41c8-a2c6-e13583ea4493
Kim, Edy Y.
f57eabf2-a422-4be5-936e-bf224cebf11e
Tuli, Aamit
9ff546f5-41cf-47af-8038-1d16fb16bb87
Sanderson, Joseph P.
55f9cdfc-ab1e-4b84-8c02-83c4d51cfcfe
Gadola, Stephan D.
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Hsu, Fong-Fu
d6827f7d-06c3-45b3-810b-5c859d0fa0e6
Besra, Gurdyal S.
b3523122-c452-4efc-b625-d80744586a47
Brenner, Michael B.
ec8181bd-a1b3-4f00-b2fb-8a7799a80797

Brennan, Patrick J., Tatituri, Raju V.V., Brigl, Manfred, Kim, Edy Y., Tuli, Aamit, Sanderson, Joseph P., Gadola, Stephan D., Hsu, Fong-Fu, Besra, Gurdyal S. and Brenner, Michael B. (2011) Invariant natural killer T cells recognise lipid self antigen induced by microbial danger signals. Nature Immunology. (doi:10.1038/ni.2143). (PMID:22037601)

Record type: Article

Abstract

Invariant natural killer T cells (iNKT cells) have a prominent role during infection and other inflammatory processes, and these cells can be activated through their T cell antigen receptors by microbial lipid antigens. However, increasing evidence shows that they are also activated in situations in which foreign lipid antigens would not be present, which suggests a role for lipid self antigen. We found that an abundant endogenous lipid, ?-D-glucopyranosylceramide (?-GlcCer), was a potent iNKT cell self antigen in mouse and human and that its activity depended on the composition of the N-acyl chain. Furthermore, ?-GlcCer accumulated during infection and in response to Toll-like receptor agonists, contributing to iNKT cell activation. Thus, we propose that recognition of ?-GlcCer by the invariant T cell antigen receptor translates innate danger signals into iNKT cell activation

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e-pub ahead of print date: 30 October 2011
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 202079
URI: https://eprints.soton.ac.uk/id/eprint/202079
ISSN: 1529-2908
PURE UUID: cc6db02d-3509-49d9-99e0-5701e3a99c74

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Date deposited: 03 Nov 2011 12:12
Last modified: 18 Jul 2017 11:11

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Contributors

Author: Patrick J. Brennan
Author: Raju V.V. Tatituri
Author: Manfred Brigl
Author: Edy Y. Kim
Author: Aamit Tuli
Author: Joseph P. Sanderson
Author: Stephan D. Gadola
Author: Fong-Fu Hsu
Author: Gurdyal S. Besra
Author: Michael B. Brenner

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