Kinetic Proofreading
T-cell receptors require N sequential phosphorylation steps. Output scales as binding-time^N — exponential amplification discriminating nearly identical ligands.
ZOT Implementation
Each receptor runs an independent KPR cascade. N consecutive above-threshold signals required to fire.
Negative Selection
In the thymus, T-cells reacting to self-antigens are deleted. Only cells that ignore self survive.
ZOT Implementation
2,000 candidates tested against 60 s of quiet substrate. >10% self-fire = killed. 500 survivors.
Adaptive KPR
Adding negative feedback to KPR creates a sharp threshold where response depends on ligand quality, not quantity.
ZOT Implementation
Feedback boost parameter. After kpr_m consecutive signals, threshold rises — filtering marginal signals.
ERK/SHP-1 Feedback
Positive ERK + negative SHP-1 feedback create a bistable switch. The cell commits fully or not at all.
ZOT Implementation
Binary quorum decision. Regulatory suppression dampens response when threat resolves.
Multi-Step Kinase
ZAP70 activation involves multiple phosphorylation steps. Each step is an additional proofreading checkpoint.
ZOT Implementation
Variable cascade depths (kpr_n = 2–6). Fast-acting catch spikes. Slow-acting catch sustained drains.
Self/Nonself Distributions
Self and nonself distributions are nearly identical. No single threshold works — population diversity is required.
ZOT Implementation
500 receptors, different sensor pairs, weights, windows. Darwinian selection keeps what works.