Speaker
Description
The paradigm of NK cell activation is the “Missing-Self Hypothesis”; NK cells kill cells that lack MHC. When considering a single interaction between an NK cell and a target cell, the “Missing-Self Hypothesis” offers a plausible explanation for NK cell activation. However, an NK cell’s interaction with a target cell is not an isolated event. Experimental studies have shown that NK cells in an MHC-deficient environment fail to lyse cells lacking MHC. Curiously, a study by the Yokoyama lab (Washington University in St. Louis) found that when 10% of cells in a well-mixed environment lacked MHC, the NK cells failed to lyse most of the cells. Our hypothesis is that target cell recognition is less about the balance of the presence or absence of markers, and more so about detecting outliers in an environment. We developed mathematical models of how NK cells assess and learn from their environment under static and dynamic MHC suppression. Our results suggest NK cells may be vulnerable to “slow growing danger” which makes detecting outliers challenging. We are collaborating with the Weis lab (Huntsman Cancer Institute) to experimentally test our model predictions.
