Researchers show how the immune system distinguishes between self molecules and non-self molecules such as those from pathogens.
A team led by the Freiburg biologists Prof. Dr. Wolfgang Schamel and Prof. Dr. Wilfried Weber conducted an experiment in which they controlled the duration of the interaction of a specific protein with T cells, a type of white blood cells, thereby showing how the immune system differentiates between self and non-self molecules. The scientists published their results in the journal eLife.
The function of the immune system is to distinguish between the body's own cells and pathogens. To protect the body from disease, it must recognize and attack these pathogens without damaging its own cells.
T cells are an important cell type of the immune system that have a central role in this process. Via their T cell receptor, they bind not only to non-self, pathogen molecules but also to their own, non-pathogenic molecules.
Exactly how T cells differentiate between self and non-self molecules is a central question in immunology. Since 1995, it has been assumed that the T cell measures how long the molecule interacts with the receptor.
If a molecule binds for a long time, it is classified as a pathogen; if it binds briefly, it is self. Because it has not yet been possible to experimentally control the duration of the binding, this hypothesis could until now neither be confirmed nor refuted.
Bioengineering, the construction of biological systems, is a major field of research of the Freiburg Signalling Research Clusters of Excellence BIOSS and CIBSS.
In the current T cell project, the researchers constructed a hybrid system in which components from humans, plants, bacteria and jellyfish are combined in order to equip the system with the desired properties.
Through this feat of engineering, it is possible to precisely control the binding duration of the T cell receptor and a synthetic ligand – in this case a photoprotein from plants – using red light as a remote control.
This use of photosensitive proteins as molecular switches is known as optogenetics. Using the OptoRobot, an optogenetic high-throughput platform, scientists have performed experiments on a large number of samples simultaneously. Thus, they have obtained accurate results and drawn meaningful conclusions for the study.
If the researchers use light conditions in which the photoprotein interacts only briefly with the T cell receptor, the T cells do not become activated. In light conditions that allow prolonged interaction, on the other hand, activation takes place. The Freiburg experiments supports the theory that T cells distinguish self and non-self, pathogenic molecules on the basis of the interaction time.
Researchers from the Clusters of Excellence BIOSS and CIBSS of the University of Freiburg, the German Cancer Research Centre and the Heidelberg University, Wageningen University in the Netherlands, and the Heinrich Heine University Düsseldorf were involved in the study.
Their results provide a better understanding of how T cells differentiate between self and non-self and may help advance immunotherapy and the treatment of autoimmunity, where the immune system attacks the body’s own tissues.
The new optogenetic system and robotics platform could also be applied to investigate other receptors and protein–protein interactions, and to provide unique insight into their activation.
Yousefi, O.S., Günther, M., Hörner, M., Chalupsky, J., Wess, M., Brandl, S.M., Smith, R.W., Fleck, C., Kunkel, T., Zurbriggen, M.D., Höfer, T., Weber, W. & Schamel, W.W.A (2019): Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor. In: eLife. DOI: 10.7554/eLife.42475.
Prof. Dr. Wolfgang Schamel
Institute of Biology III / CIBSS – Centre for Integrative Biological Signalling Studies
University of Freiburg
Nicolas Scherger | idw - Informationsdienst Wissenschaft
"Make two out of one" - Division of Artificial Cells
19.02.2020 | Max-Planck-Institut für Kolloid- und Grenzflächenforschung
Sweet beaks: What Galapagos finches and marine bacteria have in common
19.02.2020 | Max-Planck-Institut für Marine Mikrobiologie
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
19.02.2020 | Life Sciences
19.02.2020 | Information Technology
19.02.2020 | Power and Electrical Engineering