Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells
Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells
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DOI：
10.1126/science.aay9207
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发表时间：
2020-05-22
期刊：
影响因子：
56.9
通讯作者：
Dustin, M. L.
中科院分区：
文献类型：
--
作者：
Balint, S.;Muller, S.;Dustin, M. L.
细胞毒性T淋巴细胞（CTL）杀死感染和癌细胞。我们检测到细胞毒性多蛋白复合物，称为超分子攻击颗粒（SMAPs），从CTL转移到靶细胞。SMAPs从CTL中快速释放，并具有自主细胞毒性。质谱、免疫化学分析和CRISPR编辑鉴定出血小板反应蛋白-1的羧基末端片段是一种意想不到的SMAP组分，有助于靶向杀伤。直接随机光学重建显微镜解决了细胞毒性核心周围的血小板反应蛋白-1壳的直径类似于120纳米。低温软X射线断层扫描分析表明，SMAPs有一个碳致密的外壳，并存储在多核颗粒。我们认为SMAPs是自主的细胞外杀伤实体，其通过壳组分的特异性递送细胞毒性货物。
Cytotoxic T lymphocytes (CTLs) kill infected and cancerous cells. We detected transfer of cytotoxic multiprotein complexes, called supramolecular attack particles (SMAPs), from CTLs to target cells. SMAPs were rapidly released from CTLs and were autonomously cytotoxic. Mass spectrometry, immunochemical analysis, and CRISPR editing identified a carboxyl-terminal fragment of thrombospondin-1 as an unexpected SMAP component that contributed to target killing. Direct stochastic optical reconstruction microscopy resolved a cytotoxic core surrounded by a thrombospondin-1 shell of similar to 120 nanometer diameter. Cryo-soft x-ray tomography analysis revealed that SMAPs had a carbon-dense shell and were stored in multicore granules. We propose that SMAPs are autonomous extracellular killing entities that deliver cytotoxic cargo targeted by the specificity of shell components.