title: Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets.
abstract: Inhibitory receptors expressed on natural killer (NK) cells abrogate positive signals upon binding corresponding major histocompatibility complex (MHC) class I molecules on various target cells. By directly micromanipulating the effector-target cell encounter using an optical tweezers system which allowed temporal and spatial control, we demonstrate that Ly49-MHC class I interactions prevent characteristic cellular responses in NK cells upon binding to target cells. Furthermore, using this system, we directly demonstrate that an NK cell already bound to a resistant target cell may simultaneously bind and kill a susceptible target cell. Thus, although Ly49-mediated inhibitory signals can prevent many types of effector responses, they do not globally inhibit cellular function, but rather the inhibitory signal is spatially restricted towards resistant targets.
authors.affiliation: Umeå Center for Molecular Pathogenesis (UCMP), Umeå University, S-901 87 Umeå, Sweden. mikael.eriksson@ucmp.umu.se
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.forename: G
authors.initials: G
authors.lastname: Leitz
authors.forename: E
authors.initials: E
authors.lastname: Fällman
authors.forename: O
authors.initials: O
authors.lastname: Axner
authors.forename: J C
authors.initials: JC
authors.lastname: Ryan
authors.forename: M C
authors.initials: MC
authors.lastname: Nakamura
authors.forename: C L
authors.initials: CL
authors.lastname: Sentman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology; D018715:Microscopy, Video; D018448:Models, Immunological; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D015395:Histocompatibility Antigens Class I