Serial triggering of TCRs: A basis for the sensitivity and specificity of antigen recognition

Sensitivity of antigen detection by B cells correlates with high-affinity binding. This paradigm does nor appear to hold for the T-cell receptor (TCR), which is able to bind its ligand - peptide in the context of major histocompatibility complex (MHC) - with low affinity. Here, Salvatore Valitutti and Antonio Lanzavecchia propose that the efficiency of T-cell antigen recognition is dependent upon optimal kinetics of the TCR-peptide-MHC interaction, allowing serial engagements and triggering of many TCRs by a few peptide-MHC complexes.