Another view of T cell antigen recognition: Cooperative engagement of glycolipid antigens by Va14Ja18 natural TCR
Another view of T cell antigen recognition: Cooperative engagement of glycolipid antigens by Va14Ja18 natural TCR
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DOI：
10.4049/jimmunol.171.9.4539
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Joyce, S
中科院分区：
文献类型：
--
作者：
Stanic, AK;Shashidharamurthy, R;Joyce, S
Va14Ja18天然T(INKT)细胞能迅速对不同的糖脂AGS产生强烈的效应反应，并具有不同的功能结果。部分定义了控制iNKT细胞功能的生化参数。然而，iNKT细胞受体β链的影响以及α-半乳糖基神经酰胺(a-GalCer)类似物如何诱导不同的功能反应仍不清楚。利用改变的糖脂配体，我们发现iNKT细胞的Vb谱系影响识别和Ag亲和力，而亲和力不佳的Ag刺激导致高亲和力iNKT细胞的优先扩增。与iNKT细胞受体下调相关的iNKT细胞增殖和细胞因子分泌是在较窄的生化阈值内诱导的。CD1d1-α-GalCer和a-GalCer模拟负载复合体的多聚体证实了Va14Ja18 iNKT细胞受体的协同作用，其结构和/或组织似乎不同于传统的α-βTCR。我们的发现表明，iNKT细胞的功能受糖脂AGS亲和力阈值的控制，并揭示了其Ag受体装置的一个新特性，该特性可能在iNKT细胞激活中发挥重要作用。
Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of iNKT cell receptor beta-chain repertoire and how a-galactosylceramide (a-GalCer) analogues induce distinct functional responses have remained elusive. Using altered glycolipid ligands, we discovered that the Vb repertoire of iNKT cells impacts recognition and Ag avidity, and that stimulation with suboptimal avidity Ag results in preferential expansion of high-affinity iNKT cells. iNKT cell proliferation and cytokine secretion, which correlate with iNKT cell receptor down-regulation, are induced within narrow biochemical thresholds. Multimers of CD1d1-alphaGalCer- and aGalCer analogue-loaded complexes demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose structure and/or organization appear distinct from conventional alphabeta TCR. Our findings demonstrate that iNKT cell functions are controlled by affinity thresholds for glycolipid Ags and reveal a novel property of their Ag receptor apparatus that may have an important role in iNKT cell activation.