T-cell triggering is defective over a wide range of antigen doses. (A) Control F5 T cells were CFSE-labeled and transferred to Rag1^−/− hosts (3 × 10⁶/mouse), and groups of mice were challenged with a range of flu doses. At day 3, mice were culled and the responding T-cell population in the spleen analyzed by FACS. The scatter plot shows the percentage of F5 T cells triggered into division in individual mice challenged with different doses of flu virus. (B-D) F5 T cells from CD45.1⁺ control F5 and CD45.1⁻ F5 TetIL-7R mice off doxycycline 7 days were CFSE-labeled, mixed at a 1:1 ratio, and transferred (3 × 10⁶ total T cells/mouse) to groups of Rag1^−/− hosts challenged with 1.6, 6, 24, or 100 U flu virus. At day 3, mice were culled and CFSE profile of CD8⁺ TCR^hi CD45.1⁺ control (IL-7R⁺ F5) and CD45.1⁻ F5 TetIL-7R F5 T cells (IL-7R⁻ F5) analyzed by FACS. Plot shows ratio of IL-7R⁻ F5/IL-7R⁺ F5 cells triggered into division as a function of flu dose (B). Scatter plot shows percentage of F5 T cells triggered into division for IL-7R⁺ F5 (x-axis) versus IL-7R⁻ F5 (y-axis) cells in the same recipient challenged with the flu dose indicated (C). The scatter plot shows the mean division of triggered IL-7R⁺ F5 (x-axis) versus IL-7R⁻ F5 T cells in individual hosts (D). Data are pooled from 3 independent experiments.