Immature T cells get the calcium-induced jitters when they recognize self MHC, reveals a new report from Nirav Bhakta, David Oh, and Richard Lewis (Stanford University, Stanford, CA). Although jittery, the cells use calcium to stick around long enough to mature.
Immature T cells wander rapidly about the thymus, looking for antigen–MHC complexes on other cells that have just enough affinity to induce T cell selection and maturation. Productive interactions between a T cell receptor and an MHC get calcium oscillations going. Lasting oscillations turn on the transcription of selection genes, but require that the two cells interact long enough.
Now, Lewis's group shows that the same calcium oscillations also give the cells this needed time. They find that oscillations halt the wandering immature T cells in thymic slice preparations—the first 3-D environment used to study signaling during selection. “Having a calcium signal as a way of stopping cells is a kind of positive feedback,” says Lewis. “As soon as they recognize something, the calcium tells them to stop migrating.” The prolonged signaling may enhance the ability of weak interactions to trigger selection
Stopped cells were still jittery, showing small, rapid back-and-forth movements. This edge-of-leaving state might allow other signals, such as chemokines, to draw the cells away to other environments for further selection.