UCSF

As immune cells patrol our body, contacting and surveying the cells around them, they must constantly make the decision of whether or not to activate and surmount an immune response. Importantly, these choices must be made with high fidelity, as the immune cells must quickly eliminate pathogens and diseased cells while limiting damage to healthy cells. This activation decision is regulated by receptors on the immune cells that recognize distinct ligands on the surface of the cells they encounter. A hallmark of successful receptor-ligand interaction is the reorganization of these immune receptors into sub-micron and micron scale clusters, at which activation signals initiate within the immune cell. Although the importance of this receptor reorganization has been long appreciated, the mechanism by which the reorganization is achieved, how receptor reorganization promotes signal activation, and how the spatial organization of receptors regulates or modulates these binary cellular activation decisions has not been well understood. In this dissertation, I used reconstituted signaling systems to understand how the nanoscale spatial organization of the Fcγ receptor (FcγR) controls engulfment signaling in macrophages, and how the organization of the T cell receptor (TCR), inhibitory co-receptor, PD-1, and the transmembrane phosphatase, CD45, control signaling in T cells.