NK Cell Missing-Self Recognition

Target Cell Population

MHC-I expression (inhibitory) 55%

Stress-ligand density (activating) 35%

NK kill threshold θ 40%

NK Cells

Immune Synapse

No NK cell docked

Outcome Statistics

Scanned

Killed

Kill rate

Killed avg

–

Spared avg

–

MHC-I level of killed vs. spared cells

How it works

Every nucleated cell normally displays MHC class I (MHC-I) on its surface. Inhibitory NK receptors (KIR, NKG2A) bind self MHC-I and send a "don't kill" signal, while activating receptors (NKG2D, DNAM-1) bind stress-induced ligands (MICA/MICB, ULBPs) that appear on infected or transformed cells. The decision to kill is a balance of the two:

S = w_A · L_activ − w_I · L_MHC-I
kill the target when S > θ (rheostat threshold)

When a virus or tumour downregulates MHC-I to escape T cells, the inhibitory term collapses — this is the "missing-self" hypothesis (Kärre, 1986): the NK cell kills not because it recognises something foreign, but because it stops recognising "self". Many virus-infected and cancer cells also upregulate stress ligands (an "induced-self" signal), pushing S further above θ.

MHC-I expression — mean inhibitory signal across the population; lowering it mimics viral/tumour immune evasion.
Stress-ligand density — mean activating signal; raised on cells under viral or oncogenic stress.
Kill threshold θ — how "trigger-happy" the NK cell's signal integration is.
Infect random patch — carves out a cluster of cells with MHC-I sharply reduced and stress ligands raised, so you can watch the NK cells single it out.

The two comparison bars make the mechanism visible directly: killed cells should cluster at low MHC-I, spared cells at high MHC-I — exactly the signature that distinguishes missing-self recognition from random killing.

High MHC-I (self, protected) Low MHC-I (missing-self) NK cell

⚠ Couldn't load the 3D engineThree.js failed to load from the CDN. Check your connection and reload.