Abstract

Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells use polarized secretion to destroy virally infected and tumorigenic target cells. Specialised secretory lysosomes, containing the pore forming protein perforin and a series of serine proteases, termed granzymes deliver the lethal hit in a specialized domain of the immunological synapse. Our research is focused on understanding the molecular basis of polarized secretion from CTL . We have used a series of rare genetic diseases including Hermansky-Pudlak and Haemophagocytic syndromes to identify the roles of proteins involved in secretion from CTL and NK cells.

We have discovered that CTL and NK cells use a novel secretory mechanism, with the centrosome polarizing to the precise site of secretion within the immunological synapse. Our current research is aimed at understanding the basis of centrosomal localization within the immunological synapse and the mechanisms which determine secretory lysosome movement, docking and degranulation.