Interplay of cytoskeleton and surface morphology in T-cell activation

T-cells are key players in adaptive immunity. However, the critical events regulating their activation and subsequent formation of immunological synapse (IS) are not entirely understood. The focus on the genetic and biochemical characterization of immune signaling proteins has caused researchers to overlook the importance of membrane structures, the environment where underlying signaling events occur. In this project, we will combine classical approaches with state-of-art imaging technologies to investigate membrane morphology in terms of spatial organization and functional regionalization characterized by partitioning of key signaling molecules in the early stages of T-cell activation and formation of IS. We will investigate how LFA-1 and CD2 integrins, along with actin cytoskeleton and its key mechanoresponsive adapters, alpha actinin-1 and -4, control important aspects of T-cell membrane morphology. The results we obtain will provide valuable insight into how signaling modules and cytoskeleton crosstalk regulates the functional aspects of membrane morphology.