Mechanisms of secretion at the immunological synapse

Cytotoxic T lymphocytes (CTLs) and Natural Killer (NK) cells kill virally infected and tumourogenic cells. CTLs and NK cells engage directly with their 'target' cell, polarise their secretory machinery towards the point of contact, or immunological synapse (IS), and release a volley of killing agents that induce target cell apoptosis. The exocytosis oflytic granules (specialised secretory lysosomes) at the IS is highly regulated, and crucial for the delivery of apoptotic factors to the target cell. The molecular components that regulate and mediate this process are poorly characterised in eTLs and NK cells. I have shown that a Rab27a effector protein, Synaptotagminlike protein 2a, is important for the killing process. I have also investigated the expression, localisation and interactions of SNARE C§.oluble NSF ~ttachment receptor) proteins within eTLs and NK cells. Fas Ligand (FasL) is one of the lytic agents stored within lytic granules. The sorting of FasL direct to lytic granules relies upon the Src tyrosine kinase Fgr, and may require other binding partners. I have characterised the binding of SH3 domains from three different proteins, including Fgr, with the cytoplasmic tail of FasL to help establish their roles in the sorting of FasL to lytic granules.EThOS - Electronic Theses Online ServiceGBUnited Kingdo