TY - JOUR
T1 - Unique ζ-chain motifs mediate a direct TCR-actin linkage critical for immunological synapse formation and T-cell activation
AU - Klieger, Yair
AU - Almogi-Hazan, Osnat
AU - Ish-Shalom, Eliran
AU - Pato, Aviad
AU - Pauker, Maor H.
AU - Barda-Saad, Mira
AU - Wang, Lynn
AU - Baniyash, Michal
N1 - © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Actin microfilaments
KW - Immunological synapse
KW - T-cell activation
KW - TCR
UR - http://www.scopus.com/inward/record.url?scp=84892458771&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.201243099
DO - https://doi.org/10.1002/eji.201243099
M3 - مقالة
C2 - 24185712
SN - 0014-2980
VL - 44
SP - 58
EP - 68
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 1
ER -