An international team led by Goethe University Frankfurt has identified an intracellular sensor that monitors the quality of so-called MHC-I molecules, which help the immune system recognize and kill harmful cells, including tumor cells. The sensor ensures that defective MHC-I molecules remain inside the cell, where they are eventually degraded. Surprisingly, a lack of this quality assurance can lead to more MHC-I molecules reaching the surface of cancer cells, triggering a stronger immune response against the tumor.
The findings are published in the journal Cell . It is comparatively easy to tell a cell's state of health: On their surface, cells present fragments of almost all the proteins they contain inside. This means the immune system can directly recognize whether a cell has been infected by a virus or has been dangerously altered by a mutation.
Countless molecular "radio masts"—the MHC-I molecules —are responsible for presenting these fragments. They are assembled inside the cell and then transported to the membrane, the lipid layer surrounding the cell. Here, the masts are anchored such that the cargo faces outside and can be detected by troops of the immune system constantly patrolling the body.
If these troops detect harmful molecules being presented on the MHC-I radio masts, they kill the relevant cell. A requirement, however, is that the masts themselves are fully functional; otherwise, there is a risk that this mechanism will not work and harmful cells escape.