T cell receptor nanocomplexes:Cooperating clusters

The T cell antigen receptor (TCRCD3) is a multi-subunit complex responsible for triggering an adaptive immune response. It shows high specificity and sensitivity while having a low affinity for the ligand. Furthermore, T cells respond to antigen over a wide concentration range. The stoichiometry and architecture of TCR-CD3 in the membrane have been under intense scrutiny because they might be key to explaining its paradoxical properties. This review highlights new evidence that TCR-CD3 is found on intact, unstimulated T cells in monovalent (one ligand-binding site per receptor) as well as in several distinct multivalent forms. This is in contrast to the TCR-CD3 stoichiometries determined by several biochemical means, but these data can be explained by the effects of different detergents on the integrity of the receptor. Here, we discuss a model in which the multivalent receptors are important for the detection of low concentrations of ligand, and therefore confer sensitivity, whereas the co-expressed monovalent TCR-CD3s allow a wide dynamic range.