Fig. 6. The relationship between SHP-1 abundance and NK cell responsiveness.

SHP-1 is a digital regulator of NK cell responsiveness, determining the response state of a given cell. When the abundance of SHP-1 exceeds a critical threshold, as in uneducated NK cells, the EC₅₀ value for the signaling network becomes infinite and NK cells become resistant to activation, concurrently leading to the general inability to tune NK cell activity among uneducated NK cells. SHP-1 is a negative amplitude regulator in NK cell responsiveness. Subpopulations among educated NK cells with varying amounts of SHP-1 have different Pmax values (pS6), despite having consistent EC₅₀ values. The relative amounts of SHP-1 among the NK cells were established by self-MHC-class I–specific KIR and NKG2A in a dose-dependent manner for both receptors and ligands.