Relaxation Times of Ligand-Receptor Complex Formation Control T Cell Activation

Abstract

One of the most important functions of immune T cells is to recognize the presence of the pathogen-derived ligands and to quickly respond to them while at the same time not responding to its own ligands. This is known as absolute discrimination, and it is one of the most challenging phenomena to explain. The effectiveness of pathogen detection by T cell receptor is limited by chemical similarity of foreign and self-peptides and very low concentrations of foreign ligands. We propose a new mechanism of how absolute discrimination by T cells might function. It is suggested that the decision to activate or not to activate the immune response is controlled by the time to reach the stationary concentration of the T-cell-receptor-ligand-activated complex, which transfers the signal to downstream cellular biochemical networks. Our theoretical method models T cell receptor phosphorylation events as a sequence of stochastic transitions between discrete biochemical states, and this allows us to explicitly describe the dynamical properties of the system. It is found that the proposed criterion on the relaxation times is able to explain available experimental observations. In addition, we suggest that the level of stochastic noise might be an additional factor in the activation mechanisms. Furthermore, our theoretical approach explicitly analyzes the relationships between speed, sensitivity, and specificity of T cell functioning, which are the main characteristics of the process. Thus, it clarifies the molecular picture of T cell activation in immune response.