Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets

• Published in: The Journal of experimental medicine Vol. 190; no. 7; pp. 1005 - 1012
• Main Authors: Eriksson, M, Leitz, G, Fällman, E, Axner, O, Ryan, J C, Nakamura, M C, Sentman, C L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 04.10.1999
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Line; Cytotoxicity, Immunologic; Histocompatibility Antigens Class I - immunology; Killer Cells, Natural - immunology; Leukemia, Experimental - immunology; Ly-49 antigen; Ly49; major histocompatibility complex class I; Microscopy, Video; Models, Immunological; natural killer cell; optical tweezers; Original; Rats; Tumor Cells, Cultured; video microscopy
• ISSN: 0022-1007; 1540-9538; 1540-9538; 1892-1007
• DOI: 10.1084/jem.190.7.1005

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.