Faculty Opinions recommendation of Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells.

Author(s):  
Tsutomu Takeuchi ◽  
Hideto Kameda
2012 ◽  
Vol 188 (11) ◽  
pp. 5421-5427 ◽  
Author(s):  
Erin L. Filbert ◽  
Marie Le Borgne ◽  
Joseph Lin ◽  
John E. Heuser ◽  
Andrey S. Shaw

Blood ◽  
2009 ◽  
Vol 113 (1) ◽  
pp. 75-84 ◽  
Author(s):  
María Mittelbrunn ◽  
Gloria Martínez del Hoyo ◽  
María López-Bravo ◽  
Noa B. Martín-Cofreces ◽  
Alix Scholer ◽  
...  

Abstract Plasmacytoid dendritic cells (pDCs) efficiently produce type I interferon and participate in adaptive immune responses, although the molecular interactions between pDCs and antigen-specific T cells remain unknown. This study examines immune synapse (IS) formation between murine pDCs and CD4+ T cells. Mature pDCs formed canonical ISs, involving relocation to the contact site of the microtubule-organizing center, F-actin, protein kinase C-θ, and pVav, and activation of early signaling molecules in T cells. However, immature pDCs were less efficient at forming conjugates with T cells and inducing IS formation, microtubule-organizing center translocation, and T-cell signaling and activation. Time-lapse videomicroscopy and 2-photon in vivo imaging of pDC–T-cell interactions revealed that immature pDCs preferentially mediated transient interactions, whereas mature pDCs promoted more stable contacts. Our data indicate that, under steady-state conditions, pDCs preferentially establish transient contacts with naive T cells and show a very modest immunogenic capability, whereas on maturation, pDCs are able to form long-lived contacts with T cells and significantly enhance their capacity to activate these lymphocytes.


2012 ◽  
Vol 189 (5) ◽  
pp. 2159-2168 ◽  
Author(s):  
Karine Chemin ◽  
Armelle Bohineust ◽  
Stéphanie Dogniaux ◽  
Marie Tourret ◽  
Sarah Guégan ◽  
...  

2020 ◽  
Vol 13 (631) ◽  
pp. eaaz1965 ◽  
Author(s):  
Vanessa Zurli ◽  
Tommaso Montecchi ◽  
Raphael Heilig ◽  
Isabel Poschke ◽  
Michael Volkmar ◽  
...  

Understanding the costimulatory signaling that enhances the activity of cytotoxic T cells (CTLs) could identify potential targets for immunotherapy. Here, we report that CD2 costimulation plays a critical role in target cell killing by freshly isolated human CD8+ T cells, which represent a challenging but valuable model to gain insight into CTL biology. We found that CD2 stimulation critically enhanced signaling by the T cell receptor in the formation of functional immune synapses by promoting the polarization of lytic granules toward the microtubule-organizing center (MTOC). To gain insight into the underlying mechanism, we explored the CD2 signaling network by phosphoproteomics, which revealed 616 CD2-regulated phosphorylation events in 373 proteins implicated in the regulation of vesicular trafficking, cytoskeletal organization, autophagy, and metabolism. Signaling by the master metabolic regulator AMP-activated protein kinase (AMPK) was a critical node in the CD2 network, which promoted granule polarization toward the MTOC in CD8+ T cells. Granule trafficking was driven by active AMPK enriched on adjacent lysosomes, revealing previously uncharacterized signaling cross-talk between vesicular compartments in CD8+ T cells. Our results thus establish CD2 signaling as key for mediating cytotoxic killing and granule polarization in freshly isolated CD8+ T cells and strengthen the rationale to choose CD2 and AMPK as therapeutic targets to enhance CTL activity.


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