Initiation of TCR signalling revisited

T-cell receptor (TCR) multimerization has long been considered as an absolute prerequisite for T-cell activation. This view has been challenged by several recent reports showing that monomeric peptide–MHC (pMHC) complexes in solution could be stimulatory for T cells and that even a single pMHC at the immunological synapse was sufficient to trigger a T-cell Ca2+ response. Two incompatible models have been proposed to explain these new findings: the pseudodimer and the heterodimerization models. We consider that the heterodimerization model applied to adhesion-primed T cells provides an explanation for a larger set of experimental observations.