T lymphocytes are an essential component of our immune system: they have the power to eradicate infections and tumors, but, at the same time, they ensure that harmless antigens do not cause any kind of inflammation. Maintaining this balance requires multiple interactions between different types of immune cells. However, the experimental approaches available today to observe and decipher the biological significance of interactions between immune cells are very limited. This project aims to develop and exploit innovative technologies to study cell-to-cell communication in the immune system by combining methods of biological chemistry and genetic engineering with traditional immunology techniques. In particular, we are using these novel experimental approaches to trace interactions between antigen presenting cells and T cells, with the ultimate goal of revealing the molecular pathways that govern T cell response in vivo. Given the key role of T lymphocytes in various inflammatory diseases, autoimmunity, and cancer, determining the key factors that regulate this aspect of the immune response has important consequences for the development of new therapeutic approaches.