Although ezrin is tyrosine phosphorylated following TCR ligation, its biological role in T cell activation is not known. Here, we shhow that ezrin clusters at the immunological synapse upon T cell stimulation. Clustering of ezrin can be triggered by TCR ligation, or, more efficiently, by CD28 ligation. The clusters of ezrin at the immunological synapse include serine/threonine phosphorylated ezrin predominantly located within cell membrane lipid rafts. Based on these data, we propose that ezrin may play a role in the formation/stabilization of lipid raft signalosomes at the immunological synapse and therefore contribute to sustain TCR-dependent signalling.
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http://dx.doi.org/10.1016/s0165-2478(02)00075-5 | DOI Listing |
T-cell receptor recognition of cognate peptide-MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction.
View Article and Find Full Text PDFNano Lett
January 2025
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea.
Analyzing the cell interface is of paramount importance in understanding how cells interact and communicate with other cells, but an advanced analytical platform that can process complex and networked interactions between cell surface ligands and receptors is lacking. Herein, we developed the cell-interface-deciphering lipid nanotablet (CID-LNT) for multiplexed real-time cell analysis. LNT is a nanoparticle-tethered lipid bilayer chip where freely diffusing plasmonic nanoparticles induce scattering signal changes.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
March 2025
Avectas, Cherrywood Business Park, Dublin, Ireland.
Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough for the treatment of hematological malignancies. However, to treat solid tumors and certain hematologic cancers, next-generation CAR-T cells require further genetic modifications to overcome some of the current limitations. Improving manufacturing processes to preserve cell health and function of edited T cells is equally critical.
View Article and Find Full Text PDFSci Adv
January 2025
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.
View Article and Find Full Text PDFEMBO Rep
January 2025
Killer Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Cytotoxic lymphocytes are crucial to our immune system, primarily eliminating virus-infected or cancerous cells via perforin/granzyme killing. Perforin forms transmembrane pores in the plasma membrane, allowing granzymes to enter the target cell cytosol and trigger apoptosis. The prowess of cytotoxic lymphocytes to efficiently eradicate target cells has been widely harnessed in immunotherapies against haematological cancers.
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