Cell-contact dependent regulation of immune cell responses plays a vital role in balancing the need for rapid and efficient responses to a wide variety of pathological challenges, while at the same time maintaining self-tolerance. Over the last decade, our imaging studies – and those of other teams - have helped establish the emerging new paradigm that immune cell activation and inhibition is controlled by transient interactions between supramolecular assemblies of receptors, kinases and adaptors. This is a significantly different concept from a linear cascade of individual protein-protein interactions depicted in textbook diagrams of immune receptor signaling pathways.
The new challenge is to assess the heterogeneity and single-molecule level organisation of protein clusters and understand how this influences signal integration and downstream effector functions. My lab uses high- and super-resolution imaging techniques to reveal novel insights into molecular recognition by human Natural Killer cells and T cells - and how specific effector functions are realized. For example, the data revealed that remodelling of the cortical actin mesh occurs at the central region of the immune synapse. The application of new imaging technology also reveals unexpected phenomena: such as the transfer of small RNAs from immune cells into cancer cells which can serve as a new kind of immune defence.