In summary, a target cell’s presentation of self-MHC is inversely correlated to NK cell destruction of the target cell.
For example, a self MHC-I expressing cell is recognized as “self” and is saved from destruction. A cell that has lost MHC-I expression, perhaps through viral infection, is recognized as “missing-self” and destroyed. Conversely, a cell expressing foreign MHC-I is recognized as “non-self” and is destroyed.
In humans, the major histocompatibility complex is called the human leukocyte antigen (HLA). The inhibitory killer-cell immunoglobulin-like receptor (KIR) on the NK cell binds to the HLA molecules on the target cell. If there is a match between the NK cell KIR and target cell HLA, activation of inhibitory signals will save the target cell from destruction. Conversely, if there is a mismatch or missing HLA molecule, the inhibitory signal is not activated and the target cell is lysed.
Initial thoughts were that NK cells were regulated solely by inhibitory factors, but further research over the years has added another prong to NK cell function called the “induced self”. The induced self hypothesis incorporates findings which support the presence of both activating and inhibiting receptors. For example, an infected or transformed cell will express stress-induced “self” proteins, which are recognized by KIR activating receptors, and the NK cell will be activated to kill the stressed cell.
If we combine our understanding of NK cell function and the observation that many cancer cells have been observed to lose HLA expression, one can begin to see why NK cell activity is of interest to cancer researchers.
Imagine the possibilities if we are able to effectively exploit the natural activities of NK cells to specifically target and destroy cancer cells.