Figure 9. Mathematical modeling accounts for the scaling law in IL-2 dynamics.
(A) Simulated dynamics of [IL-2] for different quantities of antigen molecules, NAntigen (top) and numbers of T cells, NT cell (middle). [IL-2]max dependency with NAntigen and NT cell (bottom-filled circles) can be fitted with Equation 3 (bottom–grey plane). (B) Dependence of pSTAT5 response on NAntigen, with (top) or without (middle) TCR inhibition of pSTAT5. Abrogating TCR inhibition leads to low saturation in [IL-2]max and spurious scaling with NT cell and NAntigen (bottom). (C) Our model recaptures the acceleration of IL-2 secretion as a function of cumulative numbers of IL-2 producing cells (top). Upon removing the boost in IL-2 secretion (middle), low NT cell fail to accumulate comparable [IL-2]max to high NT cell (bottom). (D) Model prediction (top row) and experimental validation (bottom row) of IL-2 accumulation kinetics with JAK inhibitor (JAKi—solid line) or without (DMSO—dashed line) for different numbers of T cells (left) activated with different quantities of K5 peptide (right).