Characterization of the functional role of VAMP8 in granule exocytosis of T lymphocytes (69.12)

Abstract

Abstract One salient event in the adaptive immune response is the activation of T lymphocytes by foreign antigens. They patrol our body for providing a defense against intracellular pathogens, viruses and malignant cells. Upon recognition, T lymphocytes exert their cytotoxic activity through secretion of cytotoxic granules at a specialized cell interface, the immune synapse (IS), or engage in stimulus-coupled release of immune mediators in pre-formed granules. To induce target cell death, T lymphocytes rely on exocytosis of granules, which is the result of a cascade of events consisting of docking, priming, and finally Ca2+-dependent fusion involving soluble NSF attachment receptor (SNARE) proteins. VAMP8 is a SNARE protein that is a key component of a variety of secretion in other immune cell types and whose function in T cell killing is unknown. VAMP8 re-localizes to the immunological synapse following CTL activation suggesting it plays an important role in granule fusion. VAMP8 has also been shown to localize abundantly at the membranes of early and late endosomes. Additionally, VAMP8 plays a role in the exocytosis of organelles formed in the secretory pathway, such as exocrine granules and secretory lysosomes. Hence, this research is aimed at elucidating the involvement of VAMP8 in T lymphocytes of secretory granule release allowing us to better understand the contribution of VAMP8 to the killing process of T lymphocytes.