Researchers at Rockefeller University have uncovered how T cells switch from rest to attack, revealing a previously hidden motion in T cell receptors that helps explain how the immune system recognizes and responds to cancer.
Using advanced cryo-electron microscopy, the team found that the T cell receptor normally stays tightly closed and inactive. When it encounters an antigen, the receptor suddenly opens in a spring-like motion—similar to a jack-in-the-box—sending a signal that activates the immune response.
This mechanism was not seen before because earlier experiments removed the cell membrane with detergents, which caused the receptor to open too early. By studying the receptor in a more natural membrane-like environment, researchers were able to observe its true resting state for the first time.
The discovery has important medical implications. It helps explain why some T cell–based immunotherapies do not work well in certain cancers and provides new ways to fine-tune T cells to be more effective and less likely to burn out. The findings may also guide the design of better vaccines by clarifying how immune receptors interact with different targets.