Small contacts, big decisions – early signal processing by T cells

T cells are highly tactile cells that protect us from infections and cancer by reacting to complexes of peptides and major histocompatibility proteins presented by target cells. The most important decision a T cell makes is whether to respond to a potential target or move on. We have discovered that this decision is made within seconds, at a stage when the T cell has formed just a few, very small (~300 nm) ‘close contacts’ with its target using finger-like protrusions of its surface called “microvilli”. Building on this finding, we now want to understand how information gathered at contacts this small is processed by T cells, leading to dramatic changes in their behaviour. Using new methods to visualise close-contact formation, we will determine how signalling receptors are distributed in resting cells and then re-organized after first contact is made. We will then establish which cytosolic signalling effectors are recruited to the receptors triggered at the close contacts. Finally, using both quantitative methods and reconstitution-based approaches we will determine how these receptor-specific signals are generated and how they are then integrated. Our study will reveal how cells process information following contact on very small length-scales, allowing rapid changes in cell behaviour.