Effects of lipid chain lengths in α-galactosylceramides on cytokine release by natural killer T cells
Effects of lipid chain lengths in α-galactosylceramides on cytokine release by natural killer T cells
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DOI：
10.1021/ja045385q
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发表时间：
2004-10-27
影响因子：
15
通讯作者：
Savage, PB
中科院分区：
文献类型：
--
作者：
Goff, RD;Gao, Y;Savage, PB
通过CD 1蛋白的糖脂呈递已成为抗原识别的一个重要方面，并且通过CD 1d向自然杀伤T细胞呈递α-糖基神经酰胺已成为理解糖脂呈递如何影响免疫应答的中心焦点。含有相对长的脂质链的α-半乳糖神经酰胺一直是深入研究的主题，因为当由CD 1d呈递给自然杀伤T细胞时，它刺激促炎和免疫调节细胞因子的释放。利用α-半乳糖神经酰胺的有效合成，我们制备了一系列糖脂，其中脂链长度已逐渐变化。已经确定了自然杀伤T细胞对这些糖脂的反应，并且我们发现截短植物鞘氨醇脂质链增加了释放的免疫调节细胞因子的相对量。以类似的方式，α-半乳糖神经酰胺中酰基链的长度影响细胞因子释放曲线。
Glycolipid presentation by CD1 proteins has emerged as an important aspect of antigen recognition, and presentation of α-glycosylceramides by CD1d to natural killer T cells has become a central focus in understanding how glycolipid presentation can influence immune responses. An α-galactosylceramide containing relatively long lipid chains has been the subject of intense study because, when presented by CD1d to natural killer T cells, it stimulates the release of both proinflammatory and immunomodulatory cytokines. Using an efficient synthesis of α-galactosylceramides, we have prepared a series of glycolipids in which the lipid chain lengths have been incrementally varied. The responses of natural killer T cells to these glycolipids have been determined, and we have found that truncation of the phytosphingosine lipid chain increases the relative amounts of immunomodulatory cytokines released. In similar fashion, the length of the acyl chain in α-galactosylceramides influences cytokine release profiles.