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Nat Rev Immunol. 2007 Sep;7(9):737-44. Epub 2007 Aug 3.

Promiscuity and the single receptor: NKG2D.

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Robert A. Eagle and John Trowsdale are at the University of Cambridge Department of Pathology, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrookes Hospital, Hills Road, Cambridge CB2 OXY, UK.


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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