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
When fat cells change their colour
28.10.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Physics and Astronomy
28.10.2016 | Life Sciences