Research team explains important step in the activation of T-cells in the immune system

As soon as foreign substances like bacteria or viruses engage with the TCR, this binding triggers the process of phosphorylation of the receptor, activating the immune defense. Scientists were previously unable to explain how the information that binding has taken place is transmitted into the inside of the TCR. Some time ago, Alarcón and Schamel already established that the receptor undergoes a change in structure as soon as a foreign substance from the outside binds: The proline-rich region is hidden inside of the TCR, and after a binding the lower area of the receptor opens, exposing the region. By studying the proline-rich region, the scientists have now succeeded in demonstrating that this exposure is important for phosphorylation.

The team led by Alarcón changed the receptors in mice by removing the proline-rich region. Dr. Aldo Borroto in Madrid and Dr. Elaine P. Dopfer in Freiburg determined that the TCR no longer functions correctly without this region, as it is no longer phosphorylated. In a receptor that has not been changed, however, the proline-rich region binds to the adapter protein Nck after the region has been exposed. Dopfer performed an in vitro reconstruction of this interaction, thus providing quantitative evidence for the study. This was done within the EU consortium SYBILLA "Systems biology on T-cell activation", where Schamel and Alarcón are partners.

Through their joint research, the scientists in Freiburg and Madrid verified that the presence and exposure of the proline-rich region is of fundamental significance for activating the TCR, and consequently the immune defense. This finding will enable scientists to reach a more complete understanding of the process, from the binding of a foreign substance to the response from the immune system. It will now be possible to elucidate the subsequent steps, which have not yet been analyzed.

Journal reference: Journal of Immunology

Provided by Albert Ludwigs University of Freiburg