title: The evolution of natural killer cell receptors.
abstract: Natural killer (NK) cells are immune cells that play a crucial role against viral infections and tumors. To be tolerant against healthy tissue and simultaneously attack infected cells, the activity of NK cells is tightly regulated by a sophisticated array of germline-encoded activating and inhibiting receptors. The best characterized mechanism of NK cell activation is "missing self" detection, i.e., the recognition of virally infected or transformed cells that reduce their MHC expression to evade cytotoxic T cells. To monitor the expression of MHC-I on target cells, NK cells have monomorphic inhibitory receptors which interact with conserved MHC molecules. However, there are other NK cell receptors (NKRs) encoded by gene families showing a remarkable genetic diversity. Thus, NKR haplotypes contain several genes encoding for receptors with activating and inhibiting signaling, and that vary in gene content and allelic polymorphism. But if missing-self detection can be achieved by a monomorphic NKR system why have these polygenic and polymorphic receptors evolved? Here, we review the expansion of NKR receptor families in different mammal species, and we discuss several hypotheses that possibly underlie the diversification of the NK cell receptor complex, including the evolution of viral decoys, peptide sensitivity, and selective MHC-downregulation.
authors.affiliation: Theoretical Biology & Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands. paola.carrillo-bustamante@bioquant.uni-heidelberg.de.|Center for Modeling and Simulation in the Biosciences, Bio-Quant Center, Heidelberg University, Heidelberg, Germany. paola.carrillo-bustamante@bioquant.uni-heidelberg.de.
authors.forename: Paola
authors.initials: P
authors.lastname: Carrillo-Bustamante
authors.affiliation: Theoretical Biology & Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
authors.affiliation: Theoretical Biology & Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019143:Evolution, Molecular; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000502:physiology; D008322:Mammals / Q000235:genetics / Q000276:immunology; D011323:Primates / Q000235:genetics / Q000276:immunology; D055607:Receptors, Natural Killer Cell / Q000502:physiology*; D012098:Reproduction; D012377:Rodentia / Q000235:genetics / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
chemical_list: D055607:Receptors, Natural Killer Cell
keywords: Agent-based modeling; Host-pathogen co-evolution; KIR; NK cell receptors; Viral evasion