Genetics, genomics, and evolutionary biology of NKG2D ligands.
Human and mouse NKG2D ligands (NKG2DLs) are absent or only poorly expressed by most normal cells but are upregulated by cell stress, hence, alerting the immune system in case of malignancy or infection. Although these ligands are numerous and highly variable (at genetic, genomic, structural, and biochemical levels), they all belong to the major histocompatibility complex class I gene superfamily and bind to a single, invariant, receptor: NKG2D. NKG2D (CD314) is an activating receptor expressed on NK cells and subsets of T cells that have a key role in the recognition and lysis of infected and tumor cells. Here, we review the molecular diversity of NKG2DLs, discuss the increasing appreciation of their roles in a variety of medical conditions, and propose several explanations for the evolutionary force(s) that seem to drive the multiplicity and diversity of NKG2DLs while maintaining their interaction with a single invariant receptor.
ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.|Laboratoire International Associé (LIA) INSERM, Strasbourg (France) - Nagano (Japan), Strasbourg, France.|Fédération Hospitalo-Universitaire (FHU) OMICARE, Strasbourg, France.
Raphael
R
Carapito
ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.|Laboratoire International Associé (LIA) INSERM, Strasbourg (France) - Nagano (Japan), Strasbourg, France.|Fédération Hospitalo-Universitaire (FHU) OMICARE, Strasbourg, France.|Laboratoire Central d'Immunologie, Pôle de Biologie, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Seiamak
S
Bahram
D000818:Animals; D014644:Genetic Variation / Q000235:genetics / Q000276:immunology*; D023281:Genomics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008024:Ligands; D051379:Mice; D008957:Models, Genetic; D018448:Models, Immunological; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K
MICA; MICB; NKG2D; NKG2D ligands (NKG2DLs)