Cell wall glycosphingolipids Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells

Cell wall glycosphingolipids Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells
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DOI:
10.1002/eji.200526157
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发表时间:
2005-06-01
影响因子:
5.4
通讯作者:
Brutkiewicz, RR
Brutkiewicz, RR
中科院分区:
医学3区
文献类型:
--
作者:
Sriram, V;Du, WJ;Brutkiewicz, RR

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目前关于NKT细胞表征的共识是基于其以CD 1d依赖性方式对合成糖脂α-半乳糖神经酰胺(α-GalCer)的反应性。由于α-GalCer的可用性有限,因此不断寻找活化NKT细胞的CD 1d呈递配体。碳水化合物的α-端基异构性被认为是NKT细胞的CD 1d特异性活化的重要必要条件。已知革兰氏阴性、不含脂多糖的细菌少动鞘氨醇单胞菌含有鞘糖脂(GSL),其中α-异头糖连接到脂质链上。在这里,我们报告从这种细菌中提取的GSL能够以CD 1d特异性方式刺激NKT细胞。此外,负载有这种脂质提取物的可溶性CD 1d-Ig二聚体特异性结合NKT细胞(但不结合常规T细胞)。对S. paucimobilis GSL可能会导致其他天然来源的CD 1d特异性配体用于NKT细胞分析,旨在确定各种疾病状态的新疗法。
The current consensus on characterization of NKT cells is based on their reactivity to the synthetic glycolipid, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Because of the limited availability of alpha-GalCer, there is a constant search for CD1d-presented ligands that activate NKT cells. The alpha-anomericity of the carbohydrate is considered to be an important requisite for the CD1d-specific activation of NKT cells. The gram-negative, lipopolysaccharide-free bacterium Sphingomonas paucimobilis is known to contain glycosphingolipids (GSL) with alpha-anomeric sugars attached to the lipid chain. Here, we report that GSL extracted from this bacterium are able to stimulate NKT cells in a CD1d-specific manner. In addition, soluble CD1d-Ig dimers loaded with this lipid extract specifically bind to NKT cells (but not conventional T cells). Further studies on the S. paucimobilis GSL could potentially lead to other natural sources of CD1d-specific ligands useful for NKT cell analyses and aimed at identifying novel therapies for a variety of disease states.