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

First Author  Facciotti F Year  2012
Journal  Nat Immunol Volume  13
Issue  5 Pages  474-80
PubMed ID  22426352 Mgi Jnum  J:185375
Mgi Id  MGI:5428370 Doi  10.1038/ni.2245
Citation  Facciotti F, et al. (2012) Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nat Immunol 13(5):474-80
abstractText  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.
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