title: Structural basis of MHC class I recognition by natural killer cell receptors.
abstract: Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC class I (MHC-I) molecules on target cells. Two structurally distinct families of NK receptors have been identified, the immunoglobulin-like family (killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69). Recently, the three-dimensional structures of several NK receptors were determined, in free form or bound to MHC-I. These include those of unbound KIRs, NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together, these structures define the basic molecular architecture of both the immunoglobulin-like and C-type lectin-like families of NK receptors. In addition, crystal structures have been reported for the complex between Ly49A and H-2Dd, and for KIR2DL2 bound to HLA-Cw3. The complex structures provide a framework for understanding MHC-I recognition by NK receptors from both families and reveal striking differences in the nature of this recognition, despite the receptors' functional similarity.
authors.affiliation: Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville 20850, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Sawicki
authors.forename: N
authors.initials: N
authors.lastname: Dimasi
authors.forename: K
authors.initials: K
authors.lastname: Natarajan
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: D H
authors.initials: DH
authors.lastname: Margulies
authors.forename: R A
authors.initials: RA
authors.lastname: Mariuzza
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000950:Antigens, Ly; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006183:H-2 Antigens / Q000737:chemistry / Q000378:metabolism; D015236:HLA-C Antigens / Q000737:chemistry / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D055630:Receptors, NK Cell Lectin-Like; D017386:Sequence Homology, Amino Acid
chemical_list: D015703:Antigens, CD; D000950:Antigens, Ly; D002352:Carrier Proteins; D006183:H-2 Antigens; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; C515077:KIR2DL2 protein, human; C527088:Klra1 protein, mouse; C105299:LILRB1 protein, human; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D046911:Macromolecular Substances; D008565:Membrane Proteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D055630:Receptors, NK Cell Lectin-Like