T cells exert force for pMHC pull-ups

T cell signaling occurs when the T cell receptor (TCR) engages antigenic peptide-major histocompatibility complex (pMHC) on the surface of antigen presenting cells (APCs). Co-engagement with co-receptor CD4 or CD8 enhances T cell signaling, especially when less biologically active pMHC ligands are used. Previous studies have shown that the TCR–pMHC bond lifetime is prolonged by a ~10–15 pN force applied via agonist pMHC (1,2). The timing, magnitude, and duration of these intermittent forces determine the calcium fluxes triggered inside the T cell (1). Lateral motions of the engaged TCRs or pMHCs are often observed at the T cell–APC interface, suggesting that bonds of pMHC with TCR and/or CD4/8 are subjected to mechanical force as thees bonds have to bridge the intermembrane junction under relative motions. T cell-generated, TCR-mediated traction forces have been measured using traction force microscopy (3) and elastomer pillar arrays (4). However, no direct measurement of such forces at the per pMHC basis was available until the publication of Liu et al. (5).