Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination.
In contrast to T cell receptors, signal transducing cell surface membrane molecules involved in the regulation of responses by cells of the innate immune system employ structures that are encoded in the genome rather than generated by somatic recombination and that recognize either classical MHC-I molecules or their structural relatives (such as MICA, RAE-1, or H-60). Considerable progress has recently been made in our understanding of molecular recognition by such molecules based on the determination of their three-dimensional structure, either in isolation or in complex with their MHC-I ligands. Those best studied are the receptors that are expressed on natural killer (NK) cells, but others are found on populations of T cells and other hematopoietic cells. These molecules fall into two major structural classes, those of the immunoglobulin superfamily (KIRs and LIRs) and of the C-type lectin-like family (Ly49, NKG2D, and CD94/NKG2). Here we summarize, in a functional context, the structures of the murine and human molecules that have recently been determined, with emphasis on how they bind different regions of their MHC-I ligands, and how this allows the discrimination of tumor or virus-infected cells from normal cells of the host.
Natarajan
Kannan
K
Molecular Biology Section, Laboratory of Immunology, NIAID, NIH, Bethesda, Maryland 20892-1892, USA. knatarajan@niaid.nih.gov
Dimasi
Nazzareno
N
Wang
Jian
J
Mariuzza
Roy A
RA
Margulies
David H
DH
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000950:Antigens, Ly; 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; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D055630:Receptors, NK Cell Lectin-Like; D017634:Self Tolerance; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D015703:Antigens, CD; D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; C497869:KLRD1 protein, human; C497870:Klrd1 protein, mouse; C105299:LILRB1 protein, human; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D055630:Receptors, NK Cell Lectin-Like