Specialized immune cells called T cells can recognize threats and induce immune responses through T cell receptors (TCRs), but these receptors do not act alone. Multiple receptors gather together at the cell surface to cooperatively switch on T cells. “The minimum unit for triggering T lymphocyte activation is known as the TCR microcluster [TCR-MC],” explains Takashi Saito of the RIKEN Research Center for Allergy and Immunology in Yokohama. “These are the key structure for T cells to recognize antigens and become activated.”
The immune system in action
Copyright : TimVickers
At the interface between T cells and the antigen-presenting immune cells that switch them on, TCR-MCs accumulate at a structure called the central supramolecular activation cluster (cSMAC). Now, research from Saito and colleagues has revealed unexpected insights into how this accumulation occurs.
Saito and his team were the first to characterize TCR-MC function2, but they were uncertain how these clusters make their way from the periphery to the core of the cSMAC. To understand this phenomenon, they performed a series of experiments in which T cells were placed on an artificial lipid layer that mimics the membrane of an antigen-presenting cell, allowing them to microscopically visualize activation-related events at the T cell surface.
Cellular structures are reinforced by protein fibers that form a network called the cytoskeleton, and Saito and colleagues revealed that TCR-MC movement is mediated by dynein, a ‘motor protein’ that shuttles cargos along these fibers. “We knew lymphocyte activation was regulated through the cytoskeleton,” he says. “But it was most surprising that TCR complexes are physically associated with dynein and that their movement is mediated by assembling with this complex.”
Upon TCR activation, the dynein-facilitated movement drags TCR-MCs laterally along the surface of the membrane towards the cSMAC, a function previously unseen for this motor protein. Pharmacological inhibition of dynein strongly impaired migration of TCR-MCs and undermined their assembly within the cSMAC, as did the selective reduction of a key subunit of the dynein complex.
Intriguingly, the same treatments that impaired TCR-MC migration also enhanced T cell activation. Saito and colleagues therefore concluded that once these clusters reach the center of the cSMAC, they become internalized within the cell and thereby taken out of action. Saito hopes to exploit this effect by learning how the TCR-MC-dynein complex is assembled. “It would be ideal if we had a specific inhibitor of this assembly,” he says, “which could lead to stronger immune status with enhanced activation of T cells.”
The corresponding author for this highlight is based at the Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy