3' 和 4' 羟基在 alpha-半乳糖神经酰胺刺激不变自然杀伤 T 细胞中的作用。
The roles of 3' and 4' hydroxy groups in alpha-galactosylceramide stimulation of invariant natural killer T cells.
机构信息
Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan, China.
出版信息
ChemMedChem. 2009 Nov;4(11):1810-5. doi: 10.1002/cmdc.200900350.
Abstract
The marine-derived α-galactosylceramide is an exogenous ligand for natural killer T cells and leads to the secretion of both T help 1 (Th1) and Th2 cytokines. The relationship between the sugar moiety structure and invariant natural killer T (iNKT) cell stimulation ability has not been fully understood. With the series α-galactosylceramide analogues varied on C3′ and C4′ position, subjected to a murine system, we discovered that the 3′ hydroxyl is very crucial in maintaining the molecule’s immunogenicity. Any modification on this position will lead to the losing of activity. We also found that the C4′ position is not so sensitive and can tolerate some small modifications on it. Moreover, the C4′ substituted analogues induced biased Th2 cytokines release was observed.
摘要
海洋来源的α-半乳糖神经酰胺是自然杀伤 T 细胞的外源性配体，导致 T 辅助 1（Th1）和 Th2 细胞因子的分泌。糖部分结构与不变自然杀伤 T（iNKT）细胞刺激能力之间的关系尚未完全阐明。我们用一系列在 C3'和 C4'位变化的α-半乳糖神经酰胺类似物，在小鼠系统中进行研究，发现 3'羟基对于保持分子的免疫原性非常重要。该位置的任何修饰都会导致活性丧失。我们还发现 C4'位不那么敏感，可以容忍一些小的修饰。此外，观察到 C4'取代的类似物诱导偏向性 Th2 细胞因子释放。
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