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新型 NKT 细胞抗原：MCS-0208（2-(羟甲基)苯硫基-植物神经酰胺）-一种具有单个羟基的芳基植物神经酰胺化合物，可刺激 NKT 细胞。

New Paradigm in NKT Cell Antigens: MCS-0208 (2-(Hydroxymethyl)phenylthio-phytoceramide) - an Aryl-Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells.

机构信息

Medicinal Chemistry and Synthesis (MCS) Laboratory, Institut de Química Avançada de Catalunya (IQAC) Consejo Superior de Investigaciones Científicas (CSIC), C/ Jordi Girona 18-26, 08034, Barcelona, Spain.

Unit for Molecular Immunology and Inflammation, VIB-Center for Inflammation Research, Ghent, Belgium.

出版信息

ChemMedChem. 2021 Aug 19;16(16):2491-2496. doi: 10.1002/cmdc.202000992. Epub 2021 Jun 17.

DOI:10.1002/cmdc.202000992
PMID:33821540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8453509/
Abstract

Natural Killer T (NKT) cells play an important role in the immune response and can be activated by glycolipids presented by CD1d protein. We present MCS-0208, an unprecedented arylthioether-phytoceramide able to induce potent invariant NKT (iNKT) cell activation, notably when tested in human iNKT cells. This arylsphingolipid analog has a simple phenyl group containing a single hydroxyl substituent as a surrogate of the sugar ring. The phenylthioether structure contrasts with α-galactosylceramide (1), the prototypical glycolipid used to induce iNKT cell stimulation, where the galactose 2'-OH and 3'-OH substituents are accepted as the minimal footprint and considered critical for NKT T cell receptor (TCR) recognition. A computational study supports the recognition of aromatic compound by the CD1d and TCR proteins as radically new structures for NKT cell stimulation.

摘要

自然杀伤 T (NKT) 细胞在免疫反应中发挥重要作用，可被 CD1d 蛋白呈递的糖脂激活。我们介绍了 MCS-0208，这是一种前所未有的芳基硫醚-植物神经酰胺，能够诱导有效的不变自然杀伤 T (iNKT) 细胞激活，特别是在人 iNKT 细胞中进行测试时。这种芳基神经酰胺类似物具有一个简单的苯基，其中含有一个羟基取代基作为糖环的替代品。苯硫醚结构与α-半乳糖神经酰胺 (1) 形成对比，α-半乳糖神经酰胺是用于诱导 iNKT 细胞刺激的典型糖脂，其中半乳糖 2'-OH 和 3'-OH 取代基被接受为最小足迹，并被认为对 NKT T 细胞受体 (TCR) 识别至关重要。一项计算研究支持了 CD1d 和 TCR 蛋白对芳香化合物的识别，这是 NKT 细胞刺激的全新结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/486788936638/CMDC-16-2491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/80198cade465/CMDC-16-2491-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/d4786e5a5294/CMDC-16-2491-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/9b923a1df7d3/CMDC-16-2491-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/5330d2c5d1f5/CMDC-16-2491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/b990ccabc625/CMDC-16-2491-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/59b2b0d680b8/CMDC-16-2491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/486788936638/CMDC-16-2491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/80198cade465/CMDC-16-2491-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/deb308630524/CMDC-16-2491-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/a0efe5435cc8/CMDC-16-2491-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/6fb61bc0607f/CMDC-16-2491-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/823349712fd7/CMDC-16-2491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/d4786e5a5294/CMDC-16-2491-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/9b923a1df7d3/CMDC-16-2491-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/5330d2c5d1f5/CMDC-16-2491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/b990ccabc625/CMDC-16-2491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/826d4bae3a75/CMDC-16-2491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/59b2b0d680b8/CMDC-16-2491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807f/8453509/486788936638/CMDC-16-2491-g002.jpg

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本文引用的文献

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Design and Discovery of Covalent α-GalCer Derivatives as Potent CD1d Ligands.设计和发现共价 α-GalCer 衍生物作为有效的 CD1d 配体。
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