Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus
Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus
复制标题
DOI：
10.1038/ni.2245
复制
发表时间：
2012-05-01
影响因子：
30.5
通讯作者：
De Libero, Gennaro
中科院分区：
文献类型：
--
作者：
Facciotti, Federica;Ramanjaneyulu, Gundimeda S.;De Libero, Gennaro
半恒定型自然杀伤T细胞（iNKT细胞）的发育和成熟依赖于对胸腺中CD 1d限制性分子呈递的自身抗原的识别。刺激性胸腺自身脂质的性质仍然难以捉摸。我们从胸腺细胞中分离出脂质，发现醚键合的单烷基甘油磷酸盐和缩醛磷脂的前体和降解产物刺激iNKT细胞。合成类似物在激活胸腺和外周iNKT细胞中显示出高效力。缺乏过氧化物酶体酶磷酸甘油酮O-酰基转移酶（GNPAT）（合成醚脂质所必需的）的小鼠，iNKT细胞的胸腺成熟发生显著改变，胸腺和外周器官中的iNKT细胞减少，这证实了醚键合脂质作为iNKT细胞抗原的作用。因此，过氧化物酶体衍生的脂质是生成完整iNKT细胞库所需的非冗余自身抗原。
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.