Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells

被引：125

作者：

Balint, S. ^{[1
]}

Muller, S. ^{[2
]}

Fischer, R. ^{[3
]}

Kessler, B. M. ^{[3
]}

Harkiolaki, M. ^{[4
]}

Valitutti, S. ^{[2
,5
]}

Dustin, M. L. ^{[1
]}

机构：

[1] Univ Oxford, Kennedy Inst Rheumatol, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England

[2] INSERM, Canc Res Ctr Toulouse, Toulouse, France

[3] Univ Oxford, Target Discovery Inst, Nuffield Dept Med, Discovery Prote Facil, Oxford, England

[4] Diamond Light Source, Harwell Sci & Innovat Campus, Didcot, Oxon, England

[5] Inst Univ Canc Oncopole, Dept Pathol, Toulouse, France

来源：

SCIENCE | 2020年 / 368卷 / 6493期

基金：

英国惠康基金;

关键词：

LYTIC GRANULES; TARGET-CELLS; SIRP-ALPHA; GRANZYME-B; FC-GAMMA; LYMPHOCYTES; REVEALS; MICROSCOPY; PERFORIN; EXPRESSION;

D O I：

10.1126/science.aay9207

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：897 / +

页数：58

共 43 条

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Function-blocking antithrombospondin-1 monoclonal antibodies [J].