The white blood cells are responsible for defend our body against threats, keeping us alive. But how do these cells identify a threat? Inside the human body, with trillions of cells, they need to be specific and accurate. Otherwise, they start to attack us from inside. This responsibility falls on the shoulders of T-cells, agents skilled in identify harmful antigens and mark them to be destroyed. One of the biggest questions on immune cell signalling is how the T cells distinguish our own healthy cells and what is harmful for us.
During the development, the body produces millions of T-cells with different types of receptors randomly. After all, our body doesn’t know exactly what the future holds. But there is a problem with this strategy. We produce cells with receptors that identify peptides that belong to the body. During development progresses we eliminate most of the T-cells that react to such “self” molecules. However, some of them continue to circulate throughout life, protecting against infected and abnormal cells without harming the body.
What prevents the T cells from mark our healthy cells?
A new paper entitled Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor brings new evidences to this question. Weiner, an author of one of the papers, said to Quanta Magazine that “the cell could have some way of taking very, very tiny differences in the duration of the receptor binding, and amplifying that to a much larger cellular response.”
The key for immune cell signalling is the timing. Substances that bind to T-cell receptors for less than about five seconds are deemed safe, while longer-binding molecules are slated to be destroyed.
This theory, known as kinetic proofreading, isn’t new. Since 90’s some researchers proposed time as a key to the identification. However, tests of the hypothesis found suggestive correlations between binding time and the activation of T-cells, exactly as kinetic proofreading would have it, but these testing methods could not disentangle the effect of timing from the effects of other biophysical factors, such as structural changes in the molecules and differences in binding strength. Worse, researchers knew that many potentially important parameters at play that they couldn’t measure or hadn’t even considered.
New optogenetics data on immune cell signalling
Optogenetics is a field of research that uses light to control cells. There are scientists using the method to control protein-protein interactions in all kind of studies. Now two research teams are using this technology to study immune cell signalling, one based in Germany and the other in San Francisco. Despite the differences between these two studies, the researchers achieved similar results: When a binding event lasted for more than around five seconds, the T-cell became active, but it failed to do so for anything less than that.
Why this happens is still unclear. But the researchers have a hint to answer that: “From the moment a T-cell receptor binds to a molecule, a number of irreversible biochemical steps have to take place before the cell will activate. If the molecule detaches too early during this signaling cascade, everything has to start over from step one. “.
As always in science, a new answer creates several new questions. We know a little bit more than before, but we still have an entire unknown universe to explore.
Also published on Medium.