Origins of natural killer cell memory: special creation or adaptive evolution

Summary The few initial formative studies describing non‐specific and apparently spontaneous activity of natural killer (NK) cells have since multiplied into thousands of scientific reports defining their unique capacities and means of regulation. Characterization of the array of receptors that govern NK cell education and activation revealed an unexpected relationship with the major histocompatibility molecules that NK cells originally became well known for ignoring. Proceeding true to form, NK cells continue to up‐end archetypal understanding of their ever‐expanding capabilities. Discovery that the NK cell repertoire is extremely diverse and can be reshaped by particular viruses into unique subsets of adaptive NK cells challenges, or at least broadens, the definition of immunological memory. This review provides an overview of studies identifying adaptive NK cells, addressing the origins of NK cell memory and introducing the heretical concept of NK cells with extensive antigenic specificity. Whether these newly apparent properties reflect adaptive utilization of known NK cell attributes and receptors or a specially creative allocation from an undefined receptor array remains to be fully determined. The naive natural killer (NK) cell population is a diverse set of lymphocytes decorated with a variable array of germ‐line encoded inhibitory and activating receptors. Environmental influences, especially infection with cytomegalovirus, drive selection of a subset of NK cells with particular receptor expression patterns and a number of intracellular adaptations affecting their responsiveness.