How do incorrect ligands help detect a correct ligand?

Abstract

Intrigued by the response of T cell receptors to the presence of a few agonist ligands, we propose a minimal model that can achieve similar performance. The model consists of a small cluster of immobile receptors that bind reversibly to two types (correct/incorrect) of ligands in the environment, with slightly weaker binding strength for the incorrect one. It features binding-state coupling between nearest-neighbor receptors, and receptors in the bound/free states are activated/deactivated by specific enzymes, with rates that allow kinetic proofreading. It is found that, for a range of binding-state coupling strength, incorrect ligands alone cannot activate the receptors, but the binding of merely one correct ligand to a receptor is sufficient to promote the activation of other receptors via induced binding to incorrect ligands. Both response time and signal amplification increase as the receptor binding-state coupling strength increases until it reaches an optimal range to achieve the most rapid and sensitive response. These results suggest a possible mechanism for a speedy and specific response of receptors to very few correct ligands in biological and artificial systems at the subcellular scale.