Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands
Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands
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DOI：
10.1038/emboj.2009.286
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发表时间：
2009-11-18
期刊：
影响因子：
11.4
通讯作者：
Joyce, Sebastian
中科院分区：
文献类型：
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作者：
Florence, William C.;Xia, Chengfeng;Joyce, Sebastian
半不变的自然杀伤（NK）T细胞受体（NKTcr）识别由单态性CD 1d分子呈递的结构多样的糖脂抗原。虽然NKTcr的α链是不变的，但β链更多样化，但这种多样性如何使NKTcr能够识别不同的抗原，如α-连接的单糖（α-半乳糖神经酰胺和α-半乳糖二酰甘油）和β-连接的三糖（异葡萄糖三己糖神经酰胺），目前尚不清楚。我们在这里证明，NKTcrs，其不同的β链的使用，识别不同的糖脂抗原与CD 1d上的结合模式相似。然而，NKTcrs识别这些抗原内的不同表位位点，包括α-半乳糖基神经酰胺、结构相似的α-半乳糖基二酰基甘油和非常不同的isoglobotriaosylceramide。我们还表明，在NKTcr β链内的CDR环的相对作用随抗原的功能而变化。因此，虽然NKTcr典型地使用保守的对接模式，但NKTcr β链允许这些细胞识别结构多样的CD 1d限制性配体的独特方面。The EMBO Journal（2009）28，3579-3590. doi：10.1038/doj.2009.286; 2009年10月8日在线发布
The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands. The EMBO Journal (2009) 28, 3579-3590. doi:10.1038/emboj.2009.286; Published online 8 October 2009