A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells.
A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells.
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DOI：
10.1016/j.immuni.2011.02.001
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发表时间：
2011-03-25
期刊：
影响因子：
32.4
通讯作者：
Rossjohn J
中科院分区：
文献类型：
--
作者：
Wun KS;Cameron G;Patel O;Pang SS;Pellicci DG;Sullivan LC;Keshipeddy S;Young MH;Uldrich AP;Thakur MS;Richardson SK;Howell AR;Illarionov PA;Brooks AG;Besra GS;McCluskey J;Gapin L;Porcelli SA;Godfrey DI;Rossjohn J
自然杀伤 T (NKT) 细胞对多种 CD1d 限制性抗原 (Ag) 作出反应，但 NKT 细胞受体 (TCR) 区分 Ag 的基础尚不清楚。在这里，我们描述了 NKT TCR 针对几种密切相关的 Ag 的精细特异性，称为改变的糖脂配体 (AGL)，它们可以差异性地刺激 NKT 细胞。五个三元配合物的结构均显示出相似的对接。酰基链修饰不影响相互作用，但减少了 NKT 细胞增殖，表明对 Ag 加工或呈递有影响。相反，植物鞘氨醇链的截短会导致 TCR 结合的诱导拟合模式，从而影响 TCR 亲和力。糖基头基的修饰对 TCR 相互作用和相关细胞反应有直接影响，配体效力反映了相互作用的 t1/2 寿命。因此，我们为理解 AGL 的修饰如何导致 NKT 细胞的细胞反应发生显着改变提供了分子基础。
Natural Killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we describe NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t1/2 life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells.
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DOI：
10.1084/jem.192.5.741
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
通讯作者：
Kronenberg M
影响因子：
32.4
作者：
Mallevaey, Thierry;Scott-Browne, James P.;Gapin, Laurent
通讯作者：
Gapin, Laurent
影响因子：
11.4
作者：
Florence, William C.;Xia, Chengfeng;Joyce, Sebastian
通讯作者：
Joyce, Sebastian
影响因子：
2.7
作者：
Jervis, Peter J.;Veerapen, Natacha;Besra, Gurdyal S.
通讯作者：
Besra, Gurdyal S.
影响因子：
15.3
作者：
Kjer-Nielsen, L;Borg, NA;McCluskey, J
通讯作者：
McCluskey, J