DNA probes that store mechanical information reveal transient piconewton forces applied by T cells

Significance To defend against cancer and viral infections, the T cell receptor (TCR) must recognize antigens on the surface of target cells. TCR antigen recognition involves the transmission of forces which are often weak, infrequent, and short lived, and hence difficult to study. We solve this challenge by developing molecular probes that store mechanical information. This approach reveals the TCR forces when encountering different antigens, and this mechanical sampling is correlated with antigen potency. Since coreceptors are heavily involved in tuning immune function, we investigate the programmed cell death receptor 1 (PD1) and show that T cells transmit forces to this coinhibitory receptor, thus suggesting that mechanics may play a role in this important checkpoint pathway.