Modeling T-cell activation via condensation with kinetic proofreading

Abstract

T-cell receptor interactions with antigens on the surface of immune cells initiate a critical activation process through multiple phosphorylation steps, understood as a kinetic proofreading mechanism that enhances the specificity of the response. The activation process is associated with the formation of protein condensates, involving the linker of the receptor (LAT) and other signaling proteins. However, the contribution of these condensates to the remarkable sensitivity of the mechanism is not clear still. Here we develop a dynamical coarse-grained model to investigate the coupling of kinetic proofreading with condensate formation of the activation signal’s final product. We analyze characteristics such as specificity and activation speed, comparing these with traditional kinetic proofreading properties. Our findings suggest that condensation leads to a higher specificity of the synapse’s response with the same speed of activation compared to simple kinetic proofreading.