自然杀伤T（NKT）细胞被激活后迅速释放出大量不同种类的细胞因子并引起一系列免疫应答，在免疫系统中起重要作用。NKT细胞的激活依赖于对CD1d分子-糖脂类化合物抗原复合物的识别，因此发现抗原对该免疫细胞的研究非常关键，目前只有少数几个抗原被报道。高等真菌中含有多种具有免疫活性的糖脂类化合物，其中从可食性蘑菇分离的肌醇磷酸脂类化合物（GIPSL）的结构与CD1d分子的内源性配体磷酸肌醇非常类似，GIPSL的神经酰胺链与NKT细胞外源性抗原α-半乳糖神经酰胺完全一致；初步实验发现GIPSL具有免疫活性，我们推测GIPSL是一类新的NKT细胞天然外源性抗原。我们拟用聚合的方法来合成GIPSL及其降解产物，然后用免疫活性试验来证明它们是新型的NKT细胞抗原，并找到激活NKT细胞的最小结构。本项目提供新的NKT细胞天然外源性抗原，为进一步阐明NKT细胞的作用机制提供新的依据。

Natural killer T (NKT) cells are subpopulations of lymphocytes express both natural killer cell receptors and conserved semi-invariant T cell receptors. Functionally, NKT cells act as innate immune cells and also bridge the innate and acquired immune systems. Upon activation, NKT cells rapidly secrete large amounts of cytokines, such as IL-2, IL-4 and IFN-γ, thus contribute to the efficient licensing of other immune cell types to respond. The stimulation of NKT cells relies on the recognization of glycolipid antigens presented by CD1d restriction molecules. The lack of antigens for NKT cells as direct research tools makes research difficult to achieve a breakthrough. Only a few antigens are reported. A large amount of glycolipids in higer fungi indicate activity in immune response. Glycoinositolphosphingolipids (GIPSL) derived from edible mushrooms Agaricus bisporus and A. campestris are such a kind of glycolipids, whose structure is similar to phosphatidylinositol which is a CD1d ligand. The ceramide part of GIPSLs is the same as that of α-galacturonosylceramide and α-glucuronosylceramide which are NKT cell antigen . Because of their immunobioactivities and structure similarity, we conjecture GIPSLs are a new type of natural exogenous antigens for NKT cells. We plan to use a convergent synthetic strategy to prepare some GIPSLs and their degradation products. To explore whether they are new exogenous antigens for NKT cells, we would assay the biological activity of GIPSLs and their degradation products as NKT agonists. Furthermore, the minimum structure which can activate NKT cells would be found, and therefore the mechanism how the NKT cells recognize GIPSLs would be elucidated. Through this study, we try to find new antigens for NKT cells which will provide a new strategy and the theoretical basis for research on the mechanisms of NKT cells and the designation and clinical application of antigens for NKT cells.