(333b) Antigen Recognition at Immune-Cell Surfaces: Probing the Role of Mechanical Forces

One of the central problems in immunology involves molecular recognition at cell-cell interfaces. T cells and B cells directly engage other cells, and fascinating recent experiments have revealed that mechanical forces regulate processes by which they distinguish between self and foreign ligands. However, a unifying theoretical framework is missing. In this work, we develop hybrid computational models that account for key biophysical properties of immune-cell interfaces, including stochastic receptor-ligand binding kinetics, membrane mechanics, and actin-mediated forces on the membrane. We use these models to investigate how mechanical forces modulate the interactions of T cells and B cells with surface-presented antigens. We discuss our results in the context of antigen discrimination and highlight open questions in mechanoimmunology that theoretical approaches can help to address.