Enhanced TCR footprint by a novel glycolipid increases NKT-dependent tumor protection.
Enhanced TCR footprint by a novel glycolipid increases NKT-dependent tumor protection.
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DOI：
10.4049/jimmunol.1203134
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发表时间：
2013-09-15
期刊：
影响因子：
--
通讯作者：
Elewaut D
中科院分区：
文献类型：
--
作者：
Aspeslagh S;Nemčovič M;Pauwels N;Venken K;Wang J;Calenbergh SV;Zajonc DM;Elewaut D
NKT细胞是一种独特的调节性T细胞，对CD 1d呈递的结构多样的糖脂有反应。虽然以前认为NKTCR对糖脂（如α-GalCer）的识别遵循钥匙锁原理，但现在很清楚这种相互作用要灵活得多。本文报道了一系列具有更强抗肿瘤活性的α-GalCer 6″-OH类似物的结构-功能分析。令人惊讶的是，一种新的氨基甲酸酯类似物PyrC- α-GalCer与NKTCR形成了新的相互作用。这与极高水平的Th 1极化和上级抗肿瘤应答相关。这些数据突出了在糖的6″-OH位置添加芳香族部分的体内相关性，并且还表明，明智选择的接头是通过增加与CD 1d或NKTCR的结合来产生强Th 1极化糖脂的有希望的策略。
NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. While it was previously thought that recognition of glycolipids such as α-GalCer by NKTCR obeys a key-lock principle, it is now clear this interaction is much more flexible. Here, we report the structure-function analysis of a series of novel 6″-OH analogues of α-GalCer with more potent anti-tumor characteristics. Surprisingly, one the novel carbamate analogues, PyrC- α-GalCer, formed novel interactions with the NKTCR. This was associated with an extremely high level of Th1 polarization and superior anti-tumor responses. These data highlight the in vivo relevance of adding aromatic moieties to the 6″-OH position of the sugar and additionally show that judiciously chosen linkers are a promising strategy to generate strong Th1 polarizing glycolipids through increased binding either to CD1d or NKTCR.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.4
作者：
Akbari, Omid;Stock, Philippe;DeKruyff, Rosemarie H.
通讯作者：
DeKruyff, Rosemarie H.
影响因子：
5.6
作者：
Schiefner, Andre;Fujio, Masakazu;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
影响因子：
9.8
作者：
Girardi E;Yu ED;Li Y;Tarumoto N;Pei B;Wang J;Illarionov P;Kinjo Y;Kronenberg M;Zajonc DM
通讯作者：
Zajonc DM
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G