Biologists from the University Freiburg show that cholesterol prevents an immune response, even when no antigen is present
T cell receptors are an important part of the human immune system. They are able to switch their conformation from an inactive to an active state spontaneously without any antigens present. Cholesterol binds and stabilizes inactive receptors, giving it a decisive role in the activation of a T cell.
Prof. Dr. Wolfgang Schamel and Dr. Susana Minguet, immunologists from the University of Freiburg, and their team of researchers were able to demonstrate this in a study that has been recently published in the journal Immunity. Researchers previously believed that an antigen like a pathogen must bind to a T cell receptor in order to activate it, thereby triggering an immune response. “We demonstrated that it’s not the binding to an antigen that causes the switch in the conformation; it happens spontaneously,” said Schamel.
T cells are white blood cells that play an important role in the acquired immune defence. The T cell receptor, which is located in the outer membrane, recognizes antigens – in other words, foreign substances – and binds them. Such a receptor can have two different structures:
the resting T cell receptor in an inactive state, and the so-called primed receptor, which is in an active conformation. In the active state, the T cell receptor sets in motion signalling pathways in the T cell that trigger an immune response – the T cell attacks the intruder. Schamel and Minguet discovered that a T cell receptor switches between these two states, even in the absence of an antigen.
When an antigen enters an organism, it can only be bound by a primed T cell receptor, that is by a receptor in the active conformation, and not by a resting receptor. When this happens, the number of active receptors increases, and the T cell is activated. A primed receptor is sufficient to activate a T cell; no binding to an antigen is necessary.
This means that, although no antigen is present, an immune response can be erroneously triggered, if there are too many primed receptors. A certain mechanism prevents this: cholesterol, an abundant lipid in the membrane, only binds to receptors in the inactive state and thus stabilizes them. This reduces the number of T cell receptors that spontaneously can switch to the active state, and the T cell is not activated. Only when an antigen binds to a primed T cell receptor will further receptors switch from an inactive to active state and the T cell is activated.
Because only cholesterol can bind to an inactive T cell receptor, this is a specific interaction. “We are among the first researchers to be able to demonstrate a functional effect of an interaction of a lipid with a transmembrane protein,” said Schamel, adding: “This interaction regulates the conformation and hence the activity of the receptor.” The cell synthesizes the necessary cholesterol itself, meaning ingesting more or less cholesterol through food does not influence the amount of this lipid in the cell membrane.
Wolfgang Schamel is a professor at the Institute of Biology III at the University of Freiburg. He is also a member of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies and the Center for Chronic Immunodeficiency in Freiburg. Susana Minguet is a group leader in Schamel’s research lab. Also involved in the study were researchers from the German Cancer Research Center in Heidelberg and the Centro de Biología Moleclar Severo Ochoa in Madrid, Spain.
Mahima Swamy, Katharina Beck-Garcia, Esmeralda Beck-Garcia, Frederike A. Hartl, Anna Morath, O. Sascha Yousefi, Elaine Pashupati Dopfer, Eszter Molnár, Anna K. Schulze, Raquel Blanco, Aldo Borroto, Nadia Martín-Blanco, Balbino Alarcon, Thomas Höfer, Susana Minguet, Wolfgang W.A. Schamel (2016). A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation. Immunity 44 (5), 1091–1101. DOI: http://dx.doi.org/10.1016/j.immuni.2016.04.011
Prof. Dr. Wolfgang Schamel and Dr. Susana Minguet
BIOSS Centre for Biological Signalling Studies
University of Freiburg
Phone: +49 (0)761 / 203 - 67509
Rudolf-Werner Dreier | Albert-Ludwigs-Universität Freiburg im Breisgau
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Life Sciences
23.03.2018 | Materials Sciences
23.03.2018 | Process Engineering