Fig. 2 The kinetic signaling model

TCR-signaled positively selected cells first terminate CD8 gene transcription, and become CD4＋CD8low（Cd4＋Cd8－） intermediate （IM） cells. Since MHC-I TCR signaling is dependent on the CD8 coreceptor, the loss of the surface CD8 expression results in the cessation of TCR signaling, which allows IM cells to respond to IL-7, inducing the expression of Runx3d, which dictates the CD8 lineage fate. In contrast, the TCR signaling of MHC-IIselected cells is continuous, since MHC-II TCR signaling is independent of the expression of CD8. Persistent TCR signaling induces the expression of Thpok, which results in CD4 T cell development. The kinetic signaling model suggests that the duration of TCR signaling determines the CD4/CD8 lineage choice.