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.

Facciotti, F., Ramanjaneyulu, G., Lepore, M., Sansano, S., Cavallari, M., Kistowska, M., et al. (2012). Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. NATURE IMMUNOLOGY, 13(5), 474-480 [10.1038/ni.2245].

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

Facciotti F
Primo
;
2012

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.
Articolo in rivista - Articolo scientifico
iNKT cells, lipids, peroxisomes, thymic antigens, thymic selection
English
2012
13
5
474
480
none
Facciotti, F., Ramanjaneyulu, G., Lepore, M., Sansano, S., Cavallari, M., Kistowska, M., et al. (2012). Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. NATURE IMMUNOLOGY, 13(5), 474-480 [10.1038/ni.2245].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/335305
Citazioni
  • Scopus 172
  • ???jsp.display-item.citation.isi??? 159
Social impact