T-cell microvilli simulations show operation near packing limit and impact on antigen recognition.
Morgan J., Pettmann J., Dushek O., Lindsay AE.
T-cells are immune cells that continuously scan for foreign-derived antigens on the surfaces of nearly all cells, termed antigen presenting cells (APCs). They do this by dynamically extending numerous protrusions called microvilli (MV) that contain T-cell receptors (TCRs) towards the APC surface in order to scan for antigens. The number, size, and dynamics of these MV, and the complex multi-scale topography that results, play a yet unknown role in antigen recognition. We develop an anatomically informed model that confines antigen recognition to small areas representing MVs that can dynamically form and dissolve, and use the model to study how MV dynamics impact antigen sensitivity and discrimination. We find that MV surveillance reduces antigen sensitivity compared to a completely flat interface unless MV are stabilized in an antigen-dependent manner and observe that MV have only a modest impact on antigen discrimination. The model highlights that MV contacts optimise the competing demands of fast scanning speeds of the APC surface with antigen sensitivity. Our model predicts an interface packing fraction that corresponds closely to those observed experimentally, indicating that T-cells operate their MV near the limits imposed by anatomical and geometric constraints. Finally, we find that observed MV contact lifetimes can be largely influenced by conditions in the T-cell/APC interface with these lifetimes often being longer than the simulation or experimental observation period. The work highlights the role of MV in antigen recognition.