Unique ζ-chain motifs mediate a direct TCR-actin linkage critical for immunological synapse formation and T-cell activation

Yair Klieger, Osnat Almogi-Hazan, Eliran Ish-Shalom, Aviad Pato, Maor H. Pauker, Mira Barda-Saad, Lynn Wang, Michal Baniyash

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


TCR-mediated activation induces receptor microclusters that evolve to a defined immune synapse (IS). Many studies showed that actin polymerization and remodeling, which create a scaffold critical to IS formation and stabilization, are TCR mediated. However, the mechanisms controlling simultaneous TCR and actin dynamic rearrangement in the IS are yet not fully understood. Herein, we identify two novel TCR ζ-chain motifs, mediating the TCR's direct interaction with actin and inducing actin bundling. While T cells expressing the ζ-chain mutated in these motifs lack cytoskeleton (actin) associated (cska)-TCRs, they express normal levels of non-cska and surface TCRs as cells expressing wild-type ζ-chain. However, such mutant cells are unable to display activation-dependent TCR clustering, IS formation, expression of CD25/CD69 activation markers, or produce/secrete cytokine, effects also seen in the corresponding APCs. We are the first to show a direct TCR-actin linkage, providing the missing gap linking between TCR-mediated Ag recognition, specific cytoskeleton orientation toward the T-cell-APC interacting pole and long-lived IS maintenance.

Original languageEnglish
Pages (from-to)58-68
Number of pages11
JournalEuropean Journal of Immunology
Issue number1
StatePublished - Jan 2014

Bibliographical note

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
We gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles, and the Harold B. Abramson Chair in Immunology. This study was supported by the US-Israel Binational Science Foundation (BSF), The Israel Sciences Foudation (ISF), The Israeli Ministry of Health, The Israel Cancer Research Foundation (ICRF), The Joint German-Israeli Research Program (DKFZ-MOST), and by The Joseph and Matilda Melnick Funds. We thank Prof. Muhlrad for the help with establishing the sedimentation assay, and Orly Perl for helping in performing the acceptor photobleaching FRET assay.


  • Actin microfilaments
  • Immunological synapse
  • T-cell activation
  • TCR


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