Abstract

Natural Killer Cell Immune Surveillance Studied at the Single Cell Level

Bjorn Onfelt, Associate Professor, Karolinska Institute

Natural killer (NK) cells kill virus-infected or cancer cells through the release of cytotoxic granules into a tight intercellular contact. NK cell populations comprise individual cells with varying sensitivity to distinct input signals, leading to disparate responses. Many conventional methods are not fit to characterize heterogeneous populations as they measure the average response of all cells. Thus, there is a need for experimental platforms that provide single cell resolution. In addition, there are also transient and stochastic variations in functional responses at the single cell level, calling for methods that allow studies of many events over extended times. We have developed a microchip-based experimental platform enabling long-term live-cell microscopic studies of individual NK cells interacting with target cells. We study properties like migration behavior and cytotoxic response to resolve differences between NK cells, transient behavior for individual NK cells, and overall differences between NK cell populations isolated from different donors. To better understand how different ligands and their spatial distribution influence the NK cell response we use microcontact printing to create artificial immune synapses on glass substrates suitable for live-cell imaging. These experiments leads to better understanding of how the behavior of individual cells add up to give a functional response at the population level.