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


Original Article

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
Umeå Center for Molecular Pathogenesis (UCMP), Umeå University, S-901 87 Umeå, Sweden.46-90-77-80-0746-90-785-67-93

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


The online version of this article contains supplemental material.

Abbreviation used in this paper: ITIM, immune tyrosine-based inhibitory motif.

© 1999 The Rockefeller University Press


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