Affinity threshold for thymic selection through a T-cell receptor-co-receptor zipper

The affinity of the T-cell receptor (TCR) for self antigen is the basis for the selection of a useful (MHC-restricted) and safe (self-tolerant) T-cell repertoire. However, it has been difficult to understand how thymocytes measure ligand affinity and translate this signal into a cellular response. In this Opinion article, we propose a new model that describes how the TCR discriminates between low- and high-affinity ligands, which is based on the duration of TCR-ligand interactions and a 'zipper' mechanism that mediates the interaction of the TCR and co-receptor molecules to initiate negative-selection signalling.