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

DOI: 10.1126/science.aay9207 DOI Help

Authors: S. Balint (University of Oxford) , S. Müller (Cancer Research Center of Toulouse, INSERM) , R. Fischer (Target Discovery Institute, University of Oxford,) , B. M. Kessler (Target Discovery Institute, University of Oxford,) , M. Harkiolaki (Diamond Light Source) , S. Valitutti (Cancer Research Center of Toulouse, INSERM; Institut Universitaire du Cancer-Oncopole) , M. L. Dustin (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 23000

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.

Diamond Keywords: Viruses; Immunotherapy

Subject Areas: Biology and Bio-materials

Instruments: B24-Cryo Soft X-ray Tomography

Added On: 12/05/2020 15:20

Discipline Tags:

Pathogens Non-Communicable Diseases Infectious Diseases Health & Wellbeing Cancer Structural biology Life Sciences & Biotech

Technical Tags:

Imaging Tomography