Fig. 3 The basis of MHC-I-dependent positive selection

MHC-I-dependent CD8 T cell development has two steps. In the first step, positively selected DP cells become CD4＋CD8low IM cells; this is referred to as“ phase 1”. In the second step, IM cells become CD8T cells by responding cytokines such as IL-7; this is referred to as “phase 2”. Phase 1 cells are“ lineage-undefined” cells; whereas Phase 2 cells are Runx3-expressing“ CD8 lineagedefined” cells. Phase 1 is controlled by TCR signaling; thus, DP cells that express low-affinity TCRs（e.g. HYTCR） have a short phase 1 but long phase 2, while DP cells that express high-affinity TCRs（e.g. OTI-TCR） have long phase 1 but short phase 2. A longer phase 1 duration increases the cytokine responsiveness of IM cells so that the cytokine-driven duration of Phase 2 becomes shorter. As a result, the total time for positive selection is almost constant. Error-free MHC-I positive selection requires phase 1 to end within 53 hours.