Serial triggering of many T-cell receptors by a few peptide-MHC complexes

TLYMPHOCYTES can recognize and be activated by a very small number of complexes of peptide with major histocompatibility complex (MHC) molecules displayed on the surface of antigen-presenting cells (APCs)^{1, 2}. The interaction between theT-cell receptor (TCR) and its ligand has low affinity and high off-rate^3-6. Both findings suggest that an extremely small number of TCRs must be engaged in interaction with APCs and raise the question of how so few receptors can transducean activation signal. Here we show that a small number of peptide-MHC complexes can achieve a high TCR occupancy, because a single complex can serially engage andtrigger up to ∼200 TCRs. Furthermore, TCR occupancy is proportional to the T cell'sbiological response. Our findings suggest that the low affinity of the TCR can be instrumental in enabling a small number of antigenic complexes to be detected.