surface-anchored monomeric agonist pmhcs alone trigger tcr with high sensitivitysurface-anchored单体的兴奋剂pmhcs单独触发细胞具有高度的敏感性.pdfVIP

PLoS BIOLOGY Surface-Anchored Monomeric Agonist pMHCs Alone Trigger TCR with High Sensitivity 1* 2 3 1,4* Zhengyu Ma , Kim A. Sharp , Paul A. Janmey , Terri H. Finkel 1 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 3 Institute for Medicine and Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 4 The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America At the interface between T cell and antigen-presenting cell (APC), peptide antigen presented by MHC (pMHC) binds to the T cell receptor (TCR) and initiates signaling. The mechanism of TCR signal initiation, or triggering, remains unclear. An interesting aspect of this puzzle is that although soluble agonist pMHCs cannot trigger TCR even at high concentrations, the same ligands trigger TCR very efficiently on the surface of APCs. Here, using lipid bilayers or plastic-based artificial APCs with defined components, we identify the critical APC-associated factors that confer agonist pMHCs with such potency. We found that CD4þ T cells are triggered by very low numbers of monomeric agonist pMHCs anchored on fluid lipid bilayers or fixed plastic surfaces, in the absence of any other APC surface molecules. Importantly, on bilayers, plastic surfaces, or real APCs, endogenous pMHCs did not enhance TCR triggering. TCR triggering, however, crit