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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 ~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.

Original publication

DOI

10.1126/science.aay9207

Type

Journal article

Journal

Science

Publication Date

22/05/2020

Volume

368

Pages

897 - 901

Keywords

CRISPR-Cas Systems, Cytotoxicity, Immunologic, Exocytosis, Gene Editing, Granzymes, Humans, K562 Cells, Multiprotein Complexes, Perforin, T-Lymphocytes, Cytotoxic, Thrombospondin 1, Tomography, X-Ray