Promiscuity and the single receptor: NKG2D

Abstract

NKG2D (natural-killer group 2, member D) is a powerful activating receptor expressed by natural killer (NK) cells and T cells that regulates immune responses during infection, cancer and autoimmunity. NKG2D ligands comprise a diverse array of MHC-class-I-related proteins that are upregulated by cellular stress. Why is it beneficial for the host to have so many ligands for the same receptor? In this Opinion article, we propose that although competition with viruses is the most likely evolutionary drive for this diversity, there might be other explanations.

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Figure 1: NKG2D and its ligands.
Figure 2: Generation of NKG2D-ligand diversity.
Figure 3: Specialized functions of NKG2D ligands in polarized epithelial-cell layers.

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Acknowledgements

The authors thank the Isaac Newton Trust (Cambridge, UK) and Cancer Research UK for grant support to R.A.E. and the Wellcome Trust (UK) to J.T. Thanks also to D. Davis, H. Reyburn, A. Tripati, and M. Wills for critical reading of the manuscript.

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Eagle, R., Trowsdale, J. Promiscuity and the single receptor: NKG2D. Nat Rev Immunol 7, 737–744 (2007). https://doi.org/10.1038/nri2144

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