When the body is fighting an invading pathogen, white blood cells--including T cells--must respond. Now, Salk Institute researchers have imaged how vital receptors on the surface of T cells bundle together when activated.
This study, the first to visualize this process in lymph nodes, could help scientists better understand how to turn up or down the immune system's activity to treat autoimmune diseases, infections or even cancer. The results were published this week in the Proceedings of the National Academy of Sciences.
"We had seen these receptors cluster and reposition in cultured cells that were artificially stimulated in the lab, but we've never seen their natural arrangements in lymph nodes until now," says senior author Björn Lillemeier, an associate professor in Salk's Nomis Laboratories for Immunobiology and Microbial Pathogenesis, and the Waitt Advanced Biophotonics Center.
T cells are activated when receptors embedded in their outer membrane bind to other immune cells that have digested an antigen, such as a virus, bacteria or cancer cell. In turn, the activated T cells switch on cellular pathways that help the body both actively seek out and destroy the antigen and remember it for the future. In the past, by looking at T-cell receptors embedded in isolated cells under the microscope, researchers discovered that the receptors are arranged in clusters--called protein islands--that merge when the cells are activated.
Lillemeier wanted more detail on how the receptors are arranged in tissue and how that arrangement might change when the T cells are activated in living hosts. The team used a super-resolution microscope developed in the laboratory of co-senior author Hu Cang, assistant professor at Salk's Waitt Advanced Biophotonics Center and holder of the Frederick B. Rentschler Developmental Chair. This microscopy approach, called light-sheet direct stochastic optical reconstruction microscopy (dSTORM), let the researchers watch T cell receptors in the membranes of T cells in mouse lymph nodes at a resolution of approximately 50 nanometers.
The new imagery confirmed the previous observation that protein islands of T-cell receptors merge into larger "microclusters" when T cells are activated. But it also showed that, before cells are activated, the protein islands are already arranged in groups--dubbed "territories" by Lillemeier's team. "The pre-organization on the molecular level basically turns the T cell into a loaded gun," says Lillemeier.
The organization of surface receptors enables T cells to launch fast and effective immune response against antigens. Understanding how the molecular organization mediates the sensitivity of T cell responses could help researchers make the immune system more or less sensitive. In the case of autoimmune diseases, clinicians would like to turn down the immune system's activity, while turning up the activity could help fight infections or cancers.
The research could also have implications for understanding other receptors in the body, which have a wide range of functions both within and outside the immune system. "We think that most receptors on the surfaces of cells are organized like this," says Ying Hu, first author and postdoctoral researcher at the Salk Institute.
The work and the researchers involved were supported by grants from the NOMIS Foundation, the Waitt Foundation, the James B. Pendleton Charitable Trust, the National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the National Cancer Institute and the California Institute for Regenerative Medicine.
About the Salk Institute for Biological Studies:
Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: www.salk.edu
Salk Communications | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology