Please use this identifier to cite or link to this item: doi:10.22028/D291-36382
Title: Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes
Author(s): Chang, Hsin-Fang
Schirra, Claudia
Ninov, Momchil
Hahn, Ulrike
Ravichandran, Keerthana
Krause, Elmar
Becherer, Ute
Bálint, Štefan
Harkiolaki, Maria
Urlaub, Henning
Valitutti, Salvatore
Baldari, Cosima T.
Dustin, Michael L.
Jahn, Reinhard
Rettig, Jens
Language: English
Title: Nature Communications
Volume: 13
Issue: 1
Publisher/Platform: Springer Nature
Year of Publication: 2022
Free key words: Cytotoxic T cells
Imaging the immune system
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Cytotoxic T lymphocytes (CTL) kill malignant and infected cells through the directed release of cytotoxic proteins into the immunological synapse (IS). The cytotoxic protein granzyme B (GzmB) is released in its soluble form or in supramolecular attack particles (SMAP). We utilize synaptobrevin2-mRFP knock-in mice to isolate fusogenic cytotoxic granules in an unbiased manner and visualize them alone or in degranulating CTLs. We identified two classes of fusion-competent granules, single core granules (SCG) and multi core granules (MCG), with different diameter, morphology and protein composition. Functional analyses demonstrate that both classes of granules fuse with the plasma membrane at the IS. SCG fusion releases soluble GzmB. MCGs can be labelled with the SMAP marker thrombospondin-1 and their fusion releases intact SMAPs. We propose that CTLs use SCG fusion to fill the synaptic cleft with active cytotoxic proteins instantly and parallel MCG fusion to deliver latent SMAPs for delayed killing of refractory targets.
DOI of the first publication: 10.1038/s41467-022-28596-y
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-363828
ISSN: 2041-1723
Date of registration: 8-Jun-2022
Description of the related object: Supplementary information
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Physiologie
Professorship: M - Prof. Dr. Jens Rettig
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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