CTLA-4 Checkpoint Blockade: Competitive Receptor Binding

Immune Synapse

CTLA-4 receptor density 30

B7 ligand density (APC) 60

Anti-CTLA-4 checkpoint inhibitor 0%

Live Signal

CD28 occupied (costim)0%

CTLA-4 occupied (inhib)0%

T-cell activation index50%

How it works

CD28 and CTLA-4 are two receptors on a T cell that both bind the same ligand pool — B7-1/B7-2 (CD80/CD86) presented on an antigen-presenting cell (APC). CD28 delivers a "go" (costimulatory) signal; CTLA-4 delivers a "stop" (inhibitory) checkpoint signal. Each ligand-receptor pair follows standard Langmuir binding kinetics, simulated per-molecule here rather than as a mean-field average:

d[R·B7]/dt = k_on·[R]_free·[B7]_free − k_off·[R·B7]
K_d = k_off / k_on   (lower K_d = higher affinity)

CTLA-4 and CD28 have similar on-rates, but CTLA-4 dissociates from B7 far more slowly (bivalent, high-avidity binding), giving it a substantially lower K_d. Over time CTLA-4 wins a disproportionate share of the shared ligand pool even though it isn't "faster" — it just doesn't let go. This simulator uses k_off(CTLA-4) ≈ k_off(CD28)/9 to reproduce that real kinetic asymmetry.

CTLA-4 density — more inhibitory receptors on the T-cell surface competing for the same B7 pool.
B7 ligand density — how much shared ligand the APC is presenting.
Anti-CTLA-4 checkpoint inhibitor — an antibody (e.g. the ipilimumab class) that sterically occupies CTLA-4's binding site. Blocked receptors (grey) are removed from competition entirely, freeing B7 for CD28 and tipping the net signal toward T-cell activation — the actual mechanism by which checkpoint-inhibitor immunotherapy unleashes an anti-tumor T-cell response.

The activation index is a simplified readout of net signal balance: 50% = CD28 and CTLA-4 signaling roughly offset; above 50% = costimulation dominates.

CD28 (costimulatory) CTLA-4 (inhibitory) CTLA-4 blocked by drug B7 ligand (CD80/CD86)

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