Vertebrate immune systems face an astonishing challenge. They are equipped to recognize small molecular signatures, and using this information must be able to discriminate between innocuous stimuli such as self-antigens or benign commensal organisms, and pathogenic stimuli from infections and altered self (cancer). To each they must respond appropriately, either to actively maintain tolerance or to respond aggressively in a targeted and tailored manner.

T cells make up an indispensable component of this system, and to meet this challenge they undergo complex processes of selection and diversification. In this talk I will describe some examples of how mathematical modeling coupled to dedicated experiments can shed light on the mechanisms by which T cells make decisions, from their development in the thymus through to their persistence as dynamic populations encoding immunological memory.