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Specific interactions between receptors and their target ligands in thepresence of non-target ligands are crucial for biological processes such as Tcell ligand discrimination. To discriminate between the target and non-targetligands, cells have to increase specificity by amplifying the small differencesin affinity among ligands. In addition, sensitivity to ligand concentration andquick discrimination are also important to detect low amounts of target ligandsand facilitate fast cellular decision making after ligand recognition. In thiswork, we find that ultraspecificity is naturally derived from a well-knownmechanism for zero-order ultrasensitivity to concentration. We also show thatthis mechanism can produce an optimal balance of specificity, sensitivity, andquick discrimination. Furthermore, we show that a model for insensitivity tolarge number of non-terget ligands can be naturally derived from theultraspecificity model. Zero-order ultraspecificity may provide alternative wayto understand ligand discrimination from the viewpoint of the nonlinearproperties of biochemical reactions.

Balancing specificity, sensitivity and speed of ligand discrimination by zero-order ultraspecificity