Research ArticleImmunology

Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors

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Science Signaling  17 Dec 2019:
Vol. 12, Issue 612, eaaw9252
DOI: 10.1126/scisignal.aaw9252

Diversity starts at the gene level

Natural killer (NK) cells are immune cells with potent antiviral and antitumor activities. These cells express several germline-encoded inhibitory receptors (KIRs) that prevent NK cells from killing healthy cells but enable the targeting of infected and transformed cells. Using various imaging techniques and functional assays, Kennedy et al. investigated the effects of genetic diversity in KIR-encoding genes on receptor organization and activity. They found that KIRs encoded by distinct genes were present at varying abundances and in clusters of varying sizes, which led to differences in downstream signaling that affected NK cell function. Together, these data suggest that genetic diversity in KIR-encoding genes affects receptor organization, signaling, and functional outcomes.

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