This illustration was created for a feature article in the October 2011 issue of the Washington University in St. Louis Alumni Magazine article by Steve Kohler.
“Professor Wayne Yokoyama, MD, long intrigued by the function of natural killer (NK) cells, has shown that NK cells, using a “licensing strategy,” are vitally important elements of the immune system. In 2010, on the occasion of accepting the Lee C. Howley Sr. Prize for his pioneering arthritis research, Wayne M. Yokoyama, MD, told his audience that real advances in science do not come from the close application of previously known arcane facts to solve difficult problems. Rather, he said, science requires taking risks to venture completely beyond what is known, pursuing nature’s secrets that she is not inclined to reveal easily. “There is art to science,” according to Yokoyama, who holds the Sam J. and Audrey Loew Levin Chair for Research in Arthritis.
A major leap in thinking then was required to realize that NK cells bind to MHC-1 just as T-cells do, but work in the opposite fashion. “When an NK cell sees an MHC-1 molecule, it doesn’t note that there is a foreign peptide being displayed. Instead, its job is to patrol for self, and when it binds to MHC-1, the NK cell is shut off,” Yokoyama explains. “Only when the self signal is insufficient is the NK cell released from its ‘off’ condition and freed to do its work.” That’s vitally important information, because viruses have evolved to depress MHC-1 in their attempt to evade T-cells. So NK cells serve an important role as a fail-safe in the immune system, effective when another of the body’s defenses has been blinded by tricky infections.
When an NK cell sees an MHC-1 molecule, it doesn’t note that there is a foreign peptide being displayed. Instead, its job is to patrol for self, and when it binds to MHC-1, the NK cell is shut off. Only when the self signal is insufficient is the NK cell released from its ‘off’ condition and freed to do its work,” Yokoyama explains. “That’s not the whole story, however, because NK cells also need to be activated.” (Illustration by Jennifer E. Fairman, CMI, FAMI)
Read the October 2011 Washington University in St. Louis Magazine article here: Rheumatologist Cracks Molecular Mystery.