T-cells, the body's sentinels, patrol every corner of the body looking out for foreign threats such as bacteria and viruses. Receptor molecules on the T-cells identify invaders by recognizing their specific antigens, helping the T-cells discriminate attackers from the body's own cells. When they recognize a threat, the T-cells signal other parts of the immune system to confront the invader.
These T-cells use a complex process to recognize the foreign pathogens and diseased cells. In a paper published this week in the journal Cell
, researchers add a new level of understanding to that process by describing how the T-cell receptors (TCR) use mechanical contact - the forces involved in their binding to the antigens - to make decisions about whether or not the cells they encounter are threats.
"This is the first systematic study of how T-cell recognition is affected by mechanical force, and it shows that forces play an important role in the functions of T-cells," said Cheng Zhu, a Regents' professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "We think that mechanical force plays a role in almost every step of T-cell biology."
The researchers, who were supported by the National Institutes of Health, made their discoveries using a tiny sensor based on a single red blood cell and a new technique for detecting calcium ions emitted by the T-cells as part of the signaling process. They independently studied the binding of antigens to more than a hundred individual T-cells, measuring the forces involved in the binding and the lifetimes of the bonds. That information was then correlated to the calcium signaling they observed.