Our immune system is divided in two components termed ‘innate’ and ‘adaptive’ immunity.
Whereas innate immune cells orchestrate the early stages of a protective immune response,
adaptive immune cells such as T cells come into play later to fully eradicate the source of
infection. In some individuals these responses turn against the host’s own body cells, an event that subsequently leads to autoimmune diseases such as arthritis and type 1 diabetes. This project will focus on a specific cellular subset, NKT cells, that is known to bridge innate and adaptive immunity. These cells have the ability to jump-start the immune response and, in contrast to conventional T cells, react against glycolipid antigens. We showed previously that NKT cells can be targeted to prevent autoimmune arthritis and to eradicate solid tumors. This application aims to generate insight into the factors that govern early NKT cell activation in response to different glycolipid antigens. In order to study the early events NKT cells’ therapeutic potential, we will design novel NKT cell glycolipid ligands. Next, the behavior of NKT cells in response to antigen will be studied in the lymph nodes by two-photon microscopy. This advanced technique allows one to make ‘movies’ of the behavior or living cells in intact tissues. Finally we will assess the effect of certain immune genes on early NKT cell activation, the induction of NKT cell unresponsiveness and secondary effects on the conventional T cell subset.