A temporal and spatial summation model for T-cell activation: signal integration and antigen decoding

Commitment of T cells to cytokine production and proliferation requires sustained (up to several hours) T-cell receptor (TCR) signaling that is achieved through serial engagement. This article proposes a kinetic model, adopted from neurons, which is based on the local temporal summation of successive signals. This model offers an explanation for how signals originating from serially triggered TCRs are accumulated and integrated over the period required for T-cell activation, given that each TCR-evoked signal is rapidly lost. The principal innovation of this model is the suggestion that signaling intermediates produced by serially triggered TCRs are not simply sustained but are incrementally built up. Several phenomena related to T-cell behavior and self-nonself discrimination are discussed.