Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.
Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.
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DOI：
10.1016/j.immuni.2009.03.022
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发表时间：
2009-06-19
期刊：
影响因子：
32.4
通讯作者：
Porcelli, Steven A.
中科院分区：
文献类型：
--
作者：
Im, Jin S.;Arora, Pooja;Bricard, Gabriel;Molano, Alberto;Venkataswamy, Manjunatha M.;Baine, Ian;Jerud, Elliot S.;Goldberg, Michael F.;Baena, Andres;Yu, Karl O. A.;Ndonye, Rachel M.;Howell, Amy R.;Yuan, Weiming;Cresswell, Peter;Chang, Young-tae;Illarionov, Petr A.;Besra, Gurdyal S.;Porcelli, Steven A.
CD1d限制性自然杀伤T细胞(NKT细胞)具有广泛的效应和调节活性，这与它们分泌Th1和Th2细胞型细胞因子的能力有关。我们分析了NKT细胞激活Th2型细胞因子的α半乳糖神经酰胺(αGalCer)类似物的表达，以确定配体结构如何控制NKT细胞激活的结果。用一种针对Th2型细胞因子CD1d复合体的单抗来显示和定量糖脂递呈，我们发现α细胞型细胞因子偏向配体的特征是快速和直接地负载细胞表面的CD1d蛋白。这些Th2型细胞因子偏向的αGalCer类似物与CD1d结合形成的复合体显示出与抗原呈递细胞的神经节苷脂丰富的、耐洗涤剂的质膜微域不同的排斥。这些发现有助于解释糖脂配体结构的细微变化如何控制NKT细胞的促炎和抗炎活性的平衡。
CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokine-biasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and anti-inflammatory activities of NKT cells.
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影响因子：
15
作者：
Goff, RD;Gao, Y;Savage, PB
通讯作者：
Savage, PB
影响因子：
4.4
作者：
Forestier, Claire;Takaki, Toshiyuki;Porcelli, Steven A.
通讯作者：
Porcelli, Steven A.
影响因子：
4.4
作者：
Buatois, V;Baillet, M;Machy, P
通讯作者：
Machy, P
DOI：
10.2174/1568008054863772
发表时间：
2005-09-01
期刊：
Current Drug Targets - Immune Endocrine and Metabolic Disorders
影响因子：
--
作者：
Miyake, Sachiko;Yamamura, Takashi
通讯作者：
Yamamura, Takashi
DOI：
10.1084/jem.20062342
发表时间：
2007-05-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McCarthy C;Shepherd D;Fleire S;Stronge VS;Koch M;Illarionov PA;Bossi G;Salio M;Denkberg G;Reddington F;Tarlton A;Reddy BG;Schmidt RR;Reiter Y;Griffiths GM;van der Merwe PA;Besra GS;Jones EY;Batista FD;Cerundolo V
通讯作者：
Cerundolo V