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

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.

Design for fully steerable dual-trap optical tweezers.

A design for complete beam steering (in three dimensions) of one or two optical tweezers traps is presented. The two most important requirements for efficient and stable movement of an optical trap are identified. A detailed recipe for the construction of a movable optical tweezers trap that fulfills these requirements is given (exemplified with an inverted microscope). The system has been found to allow for precise and free movements of both traps in all three dimensions in a dual-trap optical tweezers configuration and to be robust and reliable, as well as forgiving of small misalignments in the optical system.