Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune cell activation under the microscope

09.02.2009
The application of sophisticated imaging techniques illuminates spatio-temporal regulation critical for T cell activation

T cells are central to an organism’s defense against invading pathogens. But scientists have long puzzled over how they are activated and regulated after pathogen recognition. Now a team of researchers, led by Takashi Saito from the RIKEN Research Center for Allergy and Immunology in Yokohama, has succeeded in imaging molecular events that are crucial for these processes.

Full activation and differentiation of T cells requires a primary signal from T cell receptors (TCRs) upon interaction with an antigen-presenting cell (APC), and a second, distinct signal transmitted through ‘costimulatory’ receptors.

The receptor CD28 plays a predominant role in T cell costimulation. CD28-mediated signals augment many T cell functions, such as cytokine production and cell proliferation.

Modulation of these costimulatory signals has been applied in clinical trials by increasing tumor immunity and reducing autoimmune diseases. But the precise roles of molecules implicated in CD28-mediated costimulatory signals and their relationship with TCR signals require clarification.

Antigen-specific T cells ‘communicate’ with APCs through an ‘immunological synapse’, which forms at their interface and contains a central (c-) and a peripheral (p-) supramolecular activation cluster (SMAC).

At initial activation, TCRs form microclusters, which contain receptors, kinases, and adaptor proteins to induce activation signals at the interface between a T cell and an APC. These microclusters translocate to the center of the interface, resulting in cSMAC formation.

The role of microcluster translocation in T cell signaling has been unclear, and the concept that they function as signaling centers for T cell activation has raised questions as to how CD28-mediated costimulation is regulated.

Using sophisticated fluorescence microscopy techniques to study CD28-mediated costimulation at the molecular level, Saito and colleagues have found that the accumulation of microclusters at cSMAC is important for T cell costimulation. CD28 is initially recruited together with TCRs to microclusters. PKCè—a protein kinase acting downstream of CD28—is also recruited to microclusters by association with CD28, thereby resulting in the initial activation of T cells.

CD28 also plays a role in retaining PKCè at a spatially unique subregion of cSMAC, leading to sustained signals for T cell activation. “Thus, costimulation is mediated by the generation of a unique costimulatory compartment in the cSMAC via the dynamic regulation of microcluster translocation,” say the researchers.

Establishing the underlying mechanisms should lead to new treatments for autoimmune diseases, such as rheumatoid arthritis and psoriasis, as well as the prevention of graft versus host disease in transplantation, more effective vaccinations, and augmented anti-tumor immunity.

Reference

1. Yokosuka, T., Kobayashi, W., Sakata-Sogawa, K., Takamatsu, M., Hashimoto-Tane, M., Dustin, M.L., Tokunaga, M. & Saito, T. Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C è translocation. Immunity 29, 589–601 (2008).

The corresponding author for this highlight is based at the RIKEN Laboratory for Cell Signaling

Saeko Okada | ResearchSEA
Further information:
http://www.rikenresearch.riken.jp/research/644/
http://www.researchsea.com

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Creating a new composite fuel for new-generation fast reactors

20.06.2018 | Materials Sciences

Game-changing finding pushes 3D-printing to the molecular limit

20.06.2018 | Materials Sciences

Could this material enable autonomous vehicles to come to market sooner?

20.06.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>