T-cell microvilli simulations show operation near packing limit and impact on antigen recognition.
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 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 of the T-cell/APC interface to elucidate the role of MV dynamics in 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 find that MV has only a modest impact on antigen discrimination. The model highlights that MV contacts optimize the competing demands of fast scanning speeds of the APC surface with antigen sensitivity and that T-cells operate their MV near the interface packing limit. 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.