The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation
Victor Pui‐Yan, Yuesong Hu, Anna Kellner, Joshua M. Brockman, Arventh Velusamy, Aaron T. Blanchard, Brian D. Evavold, R. Alon, Khalid Salaita
Abstract
T cells defend against cancer and viral infections by rapidly scanning the surface of target cells seeking specific peptide antigens. This key process in adaptive immunity is sparked upon T cell receptor (TCR) binding of antigens within cell-cell junctions stabilized by integrin (LFA-1)/intercellular adhesion molecule–1 (ICAM-1) complexes. A long-standing question in this area is whether the forces transmitted through the LFA-1/ICAM-1 complex tune T cell signaling. Here, we use spectrally encoded DNA tension probes to reveal the first maps of LFA-1 and TCR forces generated by the T cell cytoskeleton upon antigen recognition. DNA probes that control the magnitude of LFA-1 force show that F >12 pN potentiates antigen-dependent T cell activation by enhancing T cell–substrate engagement. LFA-1/ICAM-1 mechanical events with F >12 pN also enhance the discriminatory power of the TCR when presented with near cognate antigens. Overall, our results show that T cells integrate multiple channels of mechanical information through different ligand-receptor pairs to tune function.