TCR mechanobiology: torques and tunable structures linked to early T cell signaling
- 1 Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- 2 Department of Medicine, Harvard Medical School, Boston, MA, USA
- 3 Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- 4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
- 5 Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA
Mechanotransduction is a basis for receptor signaling in many biological systems. Recent data based upon optical tweezer experiments suggest that the TCR is an anisotropic mechanosensor, converting mechanical energy into biochemical signals upon specific peptide-MHC complex (pMHC) ligation. Tangential force applied along the pseudo-twofold symmetry axis of the TCR complex post-ligation results in the αβ heterodimer exerting torque on the CD3 heterodimers as a consequence of molecular movement at the T cell–APC interface. Accompanying TCR quaternary change likely fosters signaling via the lipid bilayer predicated on the magnitude and direction of the TCR–pMHC force. TCR glycans may modulate quaternary change, thereby altering signaling outcome as might the redox state of the CxxC motifs located proximal to the TM segments in the heterodimeric CD3 subunits. Predicted alterations in TCR TM segments and surrounding lipid will convert ectodomain ligation into the earliest intracellular signaling events.
Keywords: quaternary change, mechanosensor, T cell signaling, force transduction, antigen recognition
Citation: Kim ST, Shin Y, Brazin K, Mallis RJ, Sun Z-YJ, Wagner G, Lang MJ and Reinherz EL (2012) TCR mechanobiology: torques and tunable structures linked to early T cell signaling. Front. Immun. 3:76. doi: 10.3389/fimmu.2012.00076
Received: 27 January 2012; Accepted: 27 March 2012;
Published online: 18 April 2012.
Edited by:Oreste Acuto, University of Oxford, UK
Reviewed by:Oreste Acuto, University of Oxford, UK
Karsten Sauer, The Scripps Research Institute, USA
Copyright: © 2012 Kim, Shin, Brazin, Mallis, Sun, Wagner, Lang and Reinherz. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Ellis L. Reinherz, Cancer Vaccine Center Dana-Farber Cancer Institute, 77 Avenue Louis Pasteur, HIM 419, Boston, MA 02115, USA. e-mail: email@example.com