Saunders, Philippa M.Vivian, Julian P.O'Connor, Geraldine M.Sullivan, Lucy C.Pymm, PhillipRossjohn, JamieBrooks, Andrew G.2016-03-302016-03-302015-08-18Saunders, P. M., Vivian, J. P., O'Connor, G. M., Sullivan, L. C., Pymm, P., Rossjohn, J., & Brooks, A. G. (2015). A bird's eye view of NK cell receptor interactions with their MHC class I ligands. Immunological Reviews, 267(1), 148-166. doi: 10.1111/imr.1231910.1111/imr.12319http://hdl.handle.net/10034/604029This is the peer reviewed version of the following article:Saunders, P. M., Vivian, J. P., O'Connor, G. M., Sullivan, L. C., Pymm, P., Rossjohn, J., & Brooks, A. G. (2015). A bird's eye view of NK cell receptor interactions with their MHC class I ligands. Immunological Reviews, 267(1), 148-166. doi: 10.1111/imr.12319 , which has been published in final form athttp://onlinelibrary.wiley.com/doi/10.1111/imr.12319/full . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingThe surveillance of target cells by natural killer (NK) cells utilizes an ensemble of inhibitory and activating receptors, many of which interact with major histocompatibility complex (MHC) class I molecules. NK cell recognition of MHC class I proteins is important developmentally for the acquisition of full NK cell effector capacity and during target cell recognition, where the engagement of inhibitory receptors and MHC class I molecules attenuates NK cell activation. Human NK cells have evolved two broad strategies for recognition of human leukocyte antigen (HLA) class I molecules: (i) direct recognition of polymorphic classical HLA class I proteins by diverse receptor families such as the killer cell immunoglobulin-like receptors (KIRs), and (ii) indirect recognition of conserved sets of HLA class I-derived peptides displayed on the non-classical HLA-E for recognition by CD94-NKG2 receptors. In this review, we assess the structural basis for the interaction between these NK receptors and their HLA class I ligands and, using the suite of published KIR and CD94-NKG2 ternary complexes, highlight the features that allow NK cells to orchestrate the recognition of a range of different HLA class I proteins.en-USNatural Killer CellsKIRArticleImmunological Reviews