Platforms for studying cell-cell recognition by immune cells

Immune cells interact directly with other cells and make decisions by integrating information from many different receptor-ligand interactions at these cell-cell interfaces. Since they encounter a huge variety of normal and abnormal cells, they experience many different combinations and concentrations of ligands. Understanding immune responses therefore requires platforms that enable ligands to be easily manipulated. We review and compare the available platforms, focusing on T-cell recognition. Although genetically modified antigen-presenting cells (APCs) offer the most physiological system, manipulating their ligands is difficult and slow. In contrast, solid surfaces or supported lipid bilayers allow easy manipulation of ligands but lack the biophysical properties of cells, such as softness, a glycocalyx, and/or ligand mobility. A recently developed CombiCell system enables easy manipulation of ligands while conserving key biophysical properties. By comparing the advantages and limitations of each platform, we provide a framework to choose the most suitable system to study signal integration in both basic and translational contexts.