Polarized release and retroviral subversion of TCR-enriched microvesicles at the T cell immunological synapse (P6155)

Abstract

Abstract The recognition events that mediate adaptive cellular immunity depend on intercellular contacts between T cells and antigen presenting cells (APC). T cell signaling is initiated at these specialized junctions between T cells and APCs, known as the immunological synapse (IS), when surface-expressed antigen receptors (TCR) recognize peptide fragments of pathogens (pMHC) on APCs. Using high resolution optical and electron microscopy, optical-EM correlation, and electron-tomography, we show that centrally accumulated TCR at the IS is located on the surface of extracellular microvesicles that bud at the IS center and are recognized by APC bearing cognate antigen. An early endosomal-sorting complex required for transport (ESCRT) sorts TCR for inclusion in microvesicles, while terminal ESCRT components mediate scission of microvesicles from the T cell plasma membrane. The HIV polyprotein GAG co-opts this process by displacing TCR from microvesicles, resulting in release of virus-like particles at the antigen-dependent IS. We conclude that post-signaling TCR accumulates at the IS center and is released in extracellular microvesicles by an ESCRT-dependent mechanism triggered by T cell activation. These microvesicles mediate intercellular communication in immune cell collaboration, and can be co-opted by HIV GAG for viral transmission across antigen-dependent synapses.