IMMUNOLOGIC GLYCOSPHINGOLIPIDOMICS AND NKT CELL DEVELOPMENT IN MOUSE THYMUS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 不变NKT细胞是自然杀伤细胞和T细胞的杂交细胞类型，它的发育依赖于双阳性胸腺细胞通过识别CD1d提呈的天然配体而介导的胸腺正向选择。CD1d是一种非多态、非MHC、MHC样的抗原提呈分子。遗传证据表明，β-葡萄糖神经酰胺衍生的鞘糖脂(GSLS)是NKT细胞的天然配体。N-丁基脱氧半乳糖基吉利霉素(NB-DGJ)是一种特异性抑制葡萄糖神经酰胺合成酶的药物，它抑制NKT细胞的内源性配体。此外，我们和其他人发现了一种β-连接的神经鞘糖脂--异谷氨酸三糖神经酰胺(IGb3)，它是一种刺激性NKT配体。IGb3合酶基因敲除小鼠具有正常的NKT发育和功能，表明存在其他配体，并有待鉴定。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting molecule. Genetic evidence suggested that beta-glucosylceramide derived glycosphingolipids (GSLs) are natural ligands for NKT cells. N-butyldeoxygalactonojirimycin (NB-DGJ), a drug that specifically inhibits the glucosylceramide synthase, inhibits the endogenous ligands for NKT cells. Furthermore, we and others have found a beta-linked glycosphingolipid, isoglobotriaosylceramide (iGb3), is a stimulatory NKT ligand. The iGb3 synthase knockout mice have a normal NKT development and function, indicating that other ligands exist and remain to be identified.