T cells can initiate immune responses when recognising a single foreign antigen yet tolerate high densities of self-antigens. In this talk, I will focus on the basic mechanisms that underlie this remarkable antigen sensitivity and discrimination, and how we have exploited these mechanims to enhance antigen sensitivity and discrimination for immune therapies. This work has led to a new spin-out company, MatchBio Ltd, to enhance the sensitivity of CAR-T cells. Lastly, I will highlight how the work has been underpinned by a new experimental platform that allows for simple (non-genetic) manipulation of cell surface ligands (CombiCells) to study any cell-cell recognition process.