The role of syntaxin11 in cytotoxic T lymphocytes (109.26)

Abstract

Abstract Cytotoxic T Lymphocytes (CTLs) form immunological synapses (IS) with antigen presenting cells in order to kill them. Killing requires release of lytic granules which occurs via exocytosis, and is dependent on SNARE (Soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins. Syntaxin11 is a SNARE protein that is predicted to be involved in the fusion of lytic granules in CTLs, since mutations within the coding region of Syntaxin11 lead to Familial Hemophagocytic Lymphohistiocytosis (FHL4), an immune disorder caused by impaired granule exocytosis. We have investigated the contribution of Syntaxin11 to lytic granule release. We used live cell imaging to observe the trafficking of full length Syntaxin11. Using CD3 specific antibodies as a marker for a functional IS, we show that Syntaxin11 accumulates at the IS after CTL polarization and conjugation with the APC has occurred. Syntaxin11 was also associated with Munc18-2, consistent with the role of Munc18-2 as a syntaxin chaperone and as a docking factor. Using a Syntaxin11 antibody we also confirmed the subcellular localization of Syntaxin11 in fixed CTLs with confocal microscopy. Syntaxin11 was associated with Munc18-2 and CD3 at the IS in fixed CTLs, consistent with our observations in live cell imaging of CTLs. These results support the conclusion that Syntaxin11 is involved in lytic granule exocytosis.