Biology

Dr. Sudha Kumari
Irvine lab; MIT, Cambridge

Abstract:

Highly migratory helper T cells undergo immediate arrest upon encountering antigens and establish specialized T cell-antigen presenting cell (APC) conjugates termed immunological synapses. A sustained synapse is a key requirement for helper T cell activation and effector function. A number of studies over the years have investigated synapse formation, but the mechanisms that sustain such synapses remain unknown. We investigated the regulation of synapse lifetimes by examining the synaptic interface during its disassembly, using advanced microscopy methods, pharmaco-genetic perturbations and computational simulations. Our results show that encounter with antigen triggers assembly of a WASP-dependent actin architecture that generates high tension in the plane of the T cell-APC contact.  These tensional forces actively prevent synaptic disengagement. Once activated, T cells downregulate WASP and associated actin organization responsible for tension generation, leading to synapse breaking. Furthermore, WASP-dependent actin nucleation in the early phases of synapse also provides protrusive forces that are utilized by cytotoxic T cells for enhanced recognition and killing of tumor cells. Together, I shall discuss the two novel mechanical modalities at the synaptic contacts that underlie T cell immune response.