Nav: Home

A question of time

May 03, 2019

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.
-end-
Original Publication:

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.

https://elifesciences.org/articles/42475

Contact:

Institute of Biology III / CIBSS - Centre for Integrative Biological Signalling Studies University of Freiburg

University of Freiburg

Related Immune System Articles:

Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
How a fungus can cripple the immune system
An international research team led by Professor Oliver Werz of Friedrich Schiller University, Jena, has now discovered how the fungus knocks out the immune defenses, enabling a potentially fatal fungal infection to develop.
How the immune system protects us against bowel cancer
Researchers from Charité - Universitätsmedizin Berlin have discovered a protective mechanism which is used by the body to protect intestinal stem cells from turning cancerous.
How herpesviruses shape the immune system
DZIF scientists at the Helmholtz Zentrum München have developed an analytic method that can very precisely detect viral infections using immune responses.
More Immune System News and Immune System Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.