The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/10/1005/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 1005-1012

Inhibitory Receptors Alter Natural Killer Cell Interactions with Target Cells yet Allow Simultaneous Killing of Susceptible Targets*

Mikael Erikssona, Guenther Leitzb, Erik Fällmanb, Ove Axnerb, James C. Ryanc,d, Mary C. Nakamurac,d, and Charles L. Sentmana
a Umeå Center for Molecular Pathogenesis (UCMP), Umeå University, S-901 87 Umeå, Sweden
b Department of Experimental Physics, Umeå University, S-901 87 Umeå, Sweden
c Department of Medicine, University of California, San Francisco, California 94143
d Veterans Administration Medical Center, San Francisco, California 94121

Correspondence to: Mikael Eriksson, Umeå Center for Molecular Pathogenesis (UCMP), Umeå University, S-901 87 Umeå, Sweden. Tel:46-90-785-67-93 Fax:46-90-77-80-07 E-mail:mikael.eriksson{at}ucmp.umu.se.

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.

Key Words: natural killer cell, major histocompatibility complex class I, optical tweezers, Ly49, video microscopy


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