New mechanism of virus immunity controlled by the proteolysis system

Discovery and explication of an intracellular system that recognizes and guides newly synthesized and defective proteins to the degradation system

Our cells' functioning is maintained by the operation of proteins. The reactions that synthesize proteins are extremely important and we therefore naturally expect them to be accurately carried out. In fact, biology textbooks used in high school and college depict how expertly proteins are produced through the transcription and translation system, just like a finely tuned machine. However, the process of actual protein synthesis in the cell does not necessarily have a high success rate. Even our healthy cells generate a huge amount of defective proteins all the time.

A lot of newly-synthesized proteins with defective structures are targeted for their abnormality by the degradation system immediately after production. When this does not go well, however, various pathological phenomena may occur, such as neurodegenerative disease, intellectual impairment, diabetes I and II, autoimmune disease, and increased risk of cancer. Our research lab discovered a new intracellular system that recognizes newly synthesized and defective proteins and guides them to the degradation system, and endeavors to shed light on this discovered system.

The degradation products of defective proteins have recently been attracting attention. It is now known that, rather than being useless waste products, they fulfill a necessary role in the immune system. The immune cells (lymphocytes) that circulate throughout our bodies recognize peptide antigens expressed over the whole cell body surface as a self-identification (ID) number. If the peptide antigens are a proteolytic fragment (self ID) deriving from the cell’s own protein, the lymphocytes will not attack the cells. If they are a fragment of a “foreign” protein, however, those cells are subject to attack by lymphocytes. The peptide antigens targeted by the lymphocytes are the degradation products of the defective proteins that we are studying.

So, what are these degradation fragments derived from “foreign” things? A typical example of something “foreign” would be a virus that invades our cells. After viruses invade (infect) human cells, they attempt to produce proteins derived from the virus genes inside the human cell in order to create its own progeny. Since protein synthesis sometimes fails, viral proteins also produce a certain percentage of faulty proteins, and the degradation products of these, as peptide antigens deriving from something “foreign,” end up encouraging the activation of lymphocytes. The widely-promoted COVID-19 vaccines work by generating and degrading defective proteins derived from the virus in our cells to actively generate peptide antigens which are targeted by lymphocytes.

As you can see, the system for recognizing and degrading defective proteins we research is extremely important for maintaining homeostasis in living things, but many aspects of how this system works remain unclear. The university's research lab is moving proactively into fundamental research in order to serve a role in the development of new vaccines in the future.


Department of Biological Sciences