TCR-Engineered T-Cell Therapy: Peptide-MHC Recognition

TCR Affinity

Dissociation constant K_d 50 µM

Tumor Antigen

Mean pMHC copies / cell 150

MHC-I downregulated (escape) 20%

Adoptive Cell Dose

Engineered T cells infused 18

Live Readouts

Tumor cells left

–

Cells killed

Kill rate

0.0 /min

Immune escape

Engineered T cell (patrolling)
T cell — synapse forming
Tumor cell — antigen visible
Tumor cell — MHC-I downregulated

How it works

Unlike CAR-T cells, which grip a surface protein directly, a TCR-engineered T cell only fires when its receptor recognises a specific peptide fragment sitting inside an MHC-I groove on the target cell surface — the peptide-MHC (pMHC) complex. That extra layer of recognition lets TCR-T reach intracellular tumor antigens CAR-T cannot see, but it also means a tumor can hide by simply making less MHC-I.

This simulator scores every T cell–tumor cell contact with a simplified avidity / Hill-type activation model, the standard way TCR triggering strength is summarised from measured affinities:

effective density  C = pMHC_copies × (1 − MHC_downreg)
P(activation) = C^n / (K_d^n + C^n),   n ≈ 2 (cooperative "serial triggering")

K_d — lower = a tighter-binding, more sensitive engineered receptor; shifts the curve left.
pMHC copies — how strongly the tumor presents the target peptide; tumor cells vary cell-to-cell (heterogeneity).
MHC-I downregulation — the fraction of tumor cells that escaped detection by suppressing MHC-I expression, a real, clinically observed resistance mechanism.

Watch a gold ring appear when a T cell docks and forms an immunological synapse — the dwell period during which the activation probability above is evaluated once. Success kills the tumor cell; failure lets it survive and the T cell moves on to scan another target.

T cells patrol the tissue field Ring = synapse forming

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