The T-cell receptor (TCR) has no intrinsic enzymatic activity and is instead phosphorylated by the Src tyrosine kinase, Lck. There are three main explanations for how this occurs, including the kinetic-segregation (KS) model. The KS model postulates that the state of TCR phosphorylation is maintained by an equilibrium between kinases and phosphatases. This equilibrium is disturbed locally in favour of kinases when TCRs engage their ligands, owing to the exclusion of large receptor-type tyrosine phosphatases such as CD45 from the regions of contact. Importantly, the KS model predicts that TCR signaling is not strictly ligand dependent. I will discuss evidence offering strong support for the KS model, based on the crystal structure of the extracellular region of CD45, and the behaviour of the phosphatase at new structures we call “close-contacts”. We also propose that signaling by the TCR co-stimulatory receptor CD28 induced by superagonistic antibodies is also explained, at least in part, by the physical segregation of the receptor from large phosphatases. Antibody superagonism could, in principle, be harnessed clinically to dampen immune responses by activating inhibitory receptors, but I will also refer to new opportunities for therapeutic blockade of these receptors in cancer.