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Natural killer cells

A virtual pick and mix

Nature Reviews Immunology volume 13, page 845 (2013)Cite this article

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Human peripheral blood NK cells from a cohort of 5 sets of monozygotic twins and 12 unrelated healthy individuals of defined HLA and killer cell immunoglobulin-like receptor (KIR) genotypes were used in this study. The diversity of the NK cell repertoire in this cohort was analysed by mass cytometry, using a panel of 36 monoclonal antibodies that were specific for lineage markers and NK cell receptors. Classification of the cells as positive or negative for the expression of each of the 28 NK cell receptors facilitated the assessment of 268,435,456 receptor combinations and revealed a vast heterogeneity of NK cell phenotypes. No single phenotype accounted for more than 7% of the total NK cells, and only 14 of the 28 receptors analysed were expressed by NK cells in the 50 most frequent phenotype populations. As a result of the abundance of low-frequency phenotypes, the authors also used a clustering algorithm to further analyse the data.

Both analytical algorithms revealed that the distribution of inhibitory NK cell receptor expression was more similar for monozygotic twins than for unrelated individuals, which suggests that host genetics determine the inhibitory receptor repertoire. By contrast, the level and frequency of activating receptor expression on NK cells was more diverse, even between twins, which suggests that environmental factors influence activating receptor expression.

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References

  1. Horowitz, A. et al. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci. Transl. Med. http://dx.doi.org/10.1126/scitranslmed.3006702 (2013)

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Authors
  1. Olive Leavy
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Leavy, O. A virtual pick and mix. Nat Rev Immunol 13, 845 (2013). https://doi.org/10.1038/nri3566

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