Asymmetric ligand recognition by the activating natural killer cell receptor NKG2D, a symmetric homodimer.
Natural killer (NK) cells function through a diverse array of cell-surface natural killer receptors (NCRs). NCRs specific for classical and non-classical MHC class I proteins, expressed in complex patterns of inhibitory and activating isoforms on overlapping, but distinct, subsets of NK cells, play an important role in immunosurveillance against cells that have reduced MHC class I expression as a result of infection or transformation. Another NCR, NKG2D, is an activating NCR first identified on NK cells, but subsequently found on macrophages and a variety of T cell types. NKG2D ligands in rodents include the MHC class I-like proteins RAE-1 and H60 and, in humans, ULBPs and the cell stress-inducible proteins MICA and MICB. NKG2D-MIC and -RAE-1 recognition events have been implicated in anti-viral and -tumor immune responses. Crystallographic analyses of NKG2D-MICA and -RAE-1 complexes reveal an unusual mode of recognition that apparently tolerates a surprising degree of ligand plasticity while generating affinities that are among the strongest TCR- or NCR-ligand affinities, thus, far described.
Strong
Roland K
RK
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. rstrong@fhcrc.org
D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008958:Models, Molecular; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D012996:Solutions
C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D012996:Solutions