title: A Role for cis Interaction between the Inhibitory Ly49A receptor and MHC class I for natural killer cell education.
abstract: Natural killer (NK) cells show enhanced functional competence when they express inhibitory receptors specific for inherited major histocompatibility complex class I (MHC-I) molecules. Current models imply that NK cell education requires an interaction of inhibitory receptors with MHC-I expressed on other cells. However, the inhibitory Ly49A receptor can also bind MHC-I ligand on the NK cell itself (in cis). Here we describe a Ly49A variant, which can engage MHC-I expressed on other cells but not in cis. Even though this variant inhibited NK cell effector function, it failed to educate NK cells. The association with MHC-I in cis sequestered wild-type Ly49A, and this was found to relieve NK cells from a suppressive effect of unengaged Ly49A. These data explain how inhibitory MHC-I receptors can facilitate NK cell activation. They dissociate classical inhibitory from educating functions of Ly49A and suggest that cis interaction of Ly49A is necessary for NK cell education.
authors.affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland.
authors.forename: Anick
authors.initials: A
authors.lastname: Chalifour
authors.forename: Léonardo
authors.initials: L
authors.lastname: Scarpellino
authors.forename: Jonathan
authors.initials: J
authors.lastname: Back
authors.forename: Petter
authors.initials: P
authors.lastname: Brodin
authors.forename: Estelle
authors.initials: E
authors.lastname: Devèvre
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gros
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lévy
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.forename: Petter
authors.initials: P
authors.lastname: Höglund
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: Werner
authors.initials: W
authors.lastname: Held
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005434:Flow Cytometry; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D055650:NK Cell Lectin-Like Receptor Subfamily A