Grant: Project Grant

T cells are immune cells critical for protecting against microbes and cancer. When overactive, they are implicated in the development of auto-immune diseases, such as diabetes and rheumatoid arthritis. Multiple types of molecules at the surface of T cells, known as "receptors", control cell functions so that the T cells behave adequately. This regulation is in order to ensure that T cells respond strongly enough to protect against microbes and cancer, but not too strongly to avoid provoking auto-immune diseases. SLAM family receptors (SFRs) are 6 members and a few distant relatives, including CD2 and CD48. SFRs play key roles in the control of the functions of T cells and other immune cells, and are involved in human diseases. They can also be harnessed for cancer immunotherapy. Our laboratory has made fundamental contributions to this field of research over the past 20 years. However, several key questions remain about SFRs in health, diseases and as targets for therapies. In particular, the roles of the distant relatives CD2 and CD48 are poorly understood. Our recent data indicate that CD2 and CD48 play essential roles in jump starting T cell responses. We also recently uncovered that CD2 and CD48 play previously unsuspected key roles in the generation of a special type of T cells known as MAIT cells, which are implicated in the protection against microbes and in the development of autoimmune diseases. Lastly, recent data from our laboratory have suggested that one of the regular SFRs, named SLAMF6, could be used as a drug target to improve T cell functions against cancer. However, many questions remain to be addressed about SLAMF6 before this becomes a reality. The objective of our proposal is to address these important issues, in order to improve our understanding of normal immune regulation, of the role of T cells in diseases such as autoimmune conditions, and of how T cells can be best harnessed for anti-cancer immunotherapy.