近日,英国牛津大学M. L. Dustin及其团队发现由细胞毒性T细胞(CTL)释放的自主杀伤性超分子攻击颗粒。相关论文于2020年5月7日在线发表在《科学》杂志上。
细胞毒性T淋巴细胞(CTL)能够杀死感染的细胞和癌细胞。研究人员检测到了细胞毒性多蛋白复合物从CTL转移到靶细胞,并把这些复合物命名为超分子攻击颗粒(SMAP)。SMAP从CTL中迅速释放出来,并具有自发的细胞毒性。质谱分析、免疫化学分析和CRISPR编辑确定了血小板反应蛋白1的C端片段是SMAP的成分,其有助于靶标杀死。
直接随机光学重建显微镜可解析出一个细胞毒性的核心,这由约120 nm直径的血小板反应蛋白1壳所包围。低温软X射线断层扫描分析表明,SMAP具有碳密度外壳,并存储在多核颗粒中。研究人员认为,SMAP是自主的细胞外杀伤颗粒,可根据外壳成分的特异性来传递细胞毒性货物。
附:英文原文
Title: Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells
Author: . Balint, S. Müller, R. Fischer, B. M. Kessler, M. Harkiolaki, S. Valitutti, M. L. Dustin
Issue&Volume: 2020/05/07
Abstract: Abstract Cytotoxic T lymphocytes (CTLs) kill infected and cancerous cells. We detected transfer of cytotoxic multiprotein complexes from CTLs to target cells, termed supramolecular attack particles (SMAPs). SMAPs were rapidly released from CTLs and were autonomously cytotoxic. Mass spectrometry, immunochemical analysis and CRISPR editing identified a C-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 ~120 nm 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 based on specificity of shell components.
DOI: 10.1126/science.aay9207
Source: https://science.sciencemag.org/content/early/2020/05/06/science.aay9207