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J Exp Med. 1999 Oct 4;190(7):1005-12.

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

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  • 1Umeå Center for Molecular Pathogenesis (UCMP), Umeå University, S-901 87 Umeå, Sweden.


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.

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