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. 2021 Nov 22;17(11):e10560. doi: 10.15252/msb.202110560

Figure 4. An operational mathematical model explains the divergent phenotypes of 4‐1BB and CD27 based on a shared signalling mechanism but different surface receptor regulation.

Figure 4

  1. Model schematic: T‐cell receptor (TCR) and peptide‐major histocompatibility complex (pMHC) form a receptor–ligand complex that induces the cytokine response, gated by a threshold switch. At the same time, ligand binding causes downregulation of the TCR. Similarly, the co‐stimulatory TNFRSF/TNFSF receptor–ligand pair forms a complex which causes modulation of the T‐cell activation threshold, as well as downregulation of the TNFRSF. In the case of CD27, the receptor is present from the start, whereas 4‐1BB expression is induced by TCR signalling.
  2. Simulated time courses of TCR (left), CD27 (middle) and 4‐1BB (right) surface expression using the model in (A) for pMHC in the absence or presence of the respective TNFRSF ligands.
  3. Simulated cytokine dose responses for the indicated time points in the absence (left) or presence of CD70 (middle) or 4‐1BBL (right).
  4. Simulated time courses of cytokine E max in the absence or presence of CD70 or 4‐1BBL.