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Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus

Facciotti, F. and Ramanjaneyulu, G. S. and Lepore, M. and Sansano, S. and Cavallari, M. and Kistowska, M. and Forss-Petter, S. and Ni, G. and Colone, A. and Singhal, A. and Berger, J. and Xia, C. and Mori, L. and De Libero, G.. (2012) Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nature immunology, Vol. 13, H. 5. pp. 474-480.

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Official URL: http://edoc.unibas.ch/dok/A6338655

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Abstract

The development and maturation of semi-invariant natural killer T cells (iNKT cells) rely on the recognition of self antigens presented by CD1d restriction molecules in thymus. The nature of the stimulatory thymic self lipids remains elusive. We isolated lipids from thymocytes and found that ether-bonded mono-alkyl glycerophosphates and the precursors and degradation products of plasmalogens stimulated iNKT cells. Synthetic analogs showed high potency in activating thymic and peripheral iNKT cells. Mice deficient in the peroxisomal enzyme glyceronephosphate O-acyltransferase (GNPAT), essential for the synthesis of ether lipids, had significant alteration of the thymic maturation of iNKT cells and fewer iNKT cells in both thymus and peripheral organs, which confirmed the role of ether-bonded lipids as iNKT cell antigens. Thus, peroxisome-derived lipids are nonredundant self antigens required for the generation of a full iNKT cell repertoire.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero)
UniBasel Contributors:De Libero, Gennaro
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature America
ISSN:1529-2908
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:08 May 2015 08:45

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