Structural and functional aspects of the Ly49 natural killer cell receptors.
Natural killer cells are part of the first line of innate immune defence against virus-infected cells and cancer cells in the vertebrate immune system. They are called 'natural' killers because, unlike cytotoxic T cells, they do not require a previous challenge and preactivation to become active. The Ly49 NK receptors are type II transmembrane glycoproteins, structurally characterized as disulphide-linked homodimers. They share extensive homology with C-type lectins, and they are encoded by a multigene family that in mice maps on chromosome 6. A fine balance between inhibitory and activating signals regulates the function of NK cells. Inhibitory Ly49 molecules bind primarily MHC class I ligands, whereas the ligands for activating Ly49 molecules may include MHC class I, but also interestingly MHC class I-like molecules expressed by viruses, as is the case for Ly49H, which binds the m157 gene product of murine cytomegalovirus. In this study, we review the function and X-ray crystal structure of the Ly49 NK cell receptors hitherto determined (Ly49A, Ly49C and Ly49I), and the structural features of the Ly49/MHC class I interaction as revealed by the X-ray crystal structures of Ly49A/H-2Dd and the recently determined Ly49C/H-2Kb.
Dimasi
Nazzareno
N
Molecular Medicine Laboratory, Giannina Gaslini's Children's Institute, Genova, Italy. nazzarenodimasi@ospedale-gaslini.ge.it
Biassoni
Roberto
R
D000818:Animals; D000950:Antigens, Ly / Q000737:chemistry* / Q000502:physiology; D018360:Crystallography, X-Ray; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D037181:Lectins, C-Type; D051379:Mice; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011485:Protein Binding; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; C527088:Klra1 protein, mouse; C527091:Klra3 protein, mouse; C527096:Klra8 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like