Research ArticleImmunology

Genetic and Environmental Determinants of Human NK Cell Diversity Revealed by Mass Cytometry

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Science Translational Medicine  23 Oct 2013:
Vol. 5, Issue 208, pp. 208ra145
DOI: 10.1126/scitranslmed.3006702

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NK Cell Nature Versus Nurture

Natural killer (NK) cells were first discovered because of their ability to kill tumor cells without any previous exposure. However, this population is actually quite heterogeneous: Different subgroups of NK cells express different combinations of activating and inhibiting receptors that govern their specificity. Now, Horowitz et al. use mass cytometry to examine NK cell diversity in humans.

The authors examined 35 parameters simultaneously in 5 sets of monozygotic twins as well as 12 unrelated donors. They found up to 30,000 phenotypic NK cell populations in a given individual. What’s more, by comparing the twins versus unrelated donors, they determined that although genetics primarily determined inhibitory receptor expression, activating receptors were controlled by the environment. These data suggest that inhibitory receptors may contribute more to NK cell self-tolerance, whereas activating receptors may guide response to pathogens and tumors.

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