Molecular mechanism underlying natural killer cell differentiation and acquisition of target recognition

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Natural Killer (NK) cells are a small population of white blood cells that provide us a first line of defense against many types of microorganisms, viruses, and abnormal tumor cells. Activation of NK cell functions is controlled by a balance of signaling through simultaneous engagement of two groups of NK receptors (activation and inhibitory receptors) on the cell surface. There exists a multiple-step, developmental process that turns bone marrow stem cells into these specialized NK cells. Importantly, NK cells are educated to distinguish self and non-self cells during development. The latter is important in preventing mature NK cells from attacking self-tissues. The factors and the underlying mechanism involved in this developmental process remain largely unclear. This is in part due to difficulty in genetically engineering primary NK cells, and lack of experimental systems that allow us to characterize a protein's function in specific NK maturation states.