Grant: Project Grant

T cells constitute one arm of the mammalian adaptive immune system. They originate in the thymus, and thereafter patrol the body until they encounter their specific antigen in peripheral lymphoid organs. Upon activation, various signals trigger antigen-specific T cells to expand and differentiate into discrete effector subsets that perform functions tailored to the type of ongoing threat, such as infection or tumour development. Different functional T cell subsets have been characterized and the signals driving their differentiation are well known. invariant Natural Killer T (iNKT) cells are unconventional T cells that respond faster than conventional T cells and to a different class of antigens. iNKT cells respond to lipid antigens and regulate the magnitude and quality of immune responses during numerous diseases. Notably they provide immunity to pathogens and tumours. iNKT cells develop in the thymus. They can also differentiate into various functional subsets, but unlike conventional T cells, this process happens in the thymus, and may be refined in peripheral tissues. The mechanisms and signals that control iNKT cell development and differentiation remain ill-defined. Using advanced genomics and more traditional immunology approaches, we have recently generated data that challenge our current understanding of the events and signals that govern iNKT cell development and differentiation. Therefore, our goal is to establish the pathways of iNKT cell development and functional differentiation, determine how they are regulated, and characterize their function in cancer immunity. This project builds on our recent observations and long-standing interest in iNKT cell biology. Our team combines expertise in developmental and cancer immunology, advanced genomics and bioinformatics. These innovative and exciting experiments will foster our understanding of iNKT cell biology and may lead to novel ways to selectively manipulate these cells in disease.