Figure 4

Interaction outcome depends on the relative time of activation of the two cells. (A) The activation curve of a T-cell with varying m₂ values that is activated before, alongside or after a strong T-cell, m₁ = 1. The black line marks the activation curve for a single cell alone. The threshold m₂ level depends on the order of activation. If Cell2 is activated markedly (2500 minutes) before Cell1, its activation curve does not change significantly (blue). However, if the two cells are activated together the activation curve shifts to the right and the threshold m value for Cell2 increases (red, similar to Figure 2B). Thirdly, if the order reverses and Cell1 is activated a long time (2500 minutes) before Cell2, the competition is increased and the activation threshold for Cell2 is shifted to even higher values. (B) Time dependent competition in a representative case (m₁ = 0.65 and m₂ = 1). Cell1 is activated at time 0, and after Δt minutes, Cell2 is activated. A critical time window for competition exists: if Cell2 (green line) is activated within the time window, it excludes the weaker Cell1 (black line). However, if Cell2 is activated after the window closes, it is unable to suppress Cell1, and the two coexist. (C) The length of the critical time window increases with the difference in activation strengths of the two cells. The line represent the calculated time window for exclusion, for the case of a cell with m₁ = 0.65 activated at time 0, interacting with a stronger cell (m₂ = m₁+ Δm) that is activated later. The scenario shown in (B) is marked by a black dot. (D) Simulated normalized interaction index, C, of two interacting cells, for 3 different time delays: Cell2 is activated with a delay of Δt = 0, 1250, 2500 minutes after Cell1. Color bar is the same for all panels. Note changes in both competition and cooperation behaviors over time. For example, when Cell1 is above threshold, the ability of a stronger Cell2 to exclude it diminishes with time (top row, blue patch in upper right quadrant). The black dot marks the case of m₁ = 0.65 and m₂ = 1 that is illustrated in (B).