Dr. Roffler, Steve R. 's publons link picture

Dr. Roffler, Steve R.

Distinguished Research Fellow
Division Chief
  • 02-2652-3079 (Lab) (Room No: N233)
  • 02-2782-9142 (Fax)

  1. Antibody Engineering
  2. Directed Molecular Evolution
  3. Prodrugs

Education and Positions:
  • Ph.D. University of California, Berkeley

Highlight Detail

The interplay between membrane topology and mechanical forces in regulating T cell receptor activity

Dr. Roffler, Steve R.
Communications Biology, Jan 11, 2022




T cells are critically important for host defense against infections. T cell activation is specific because signal initiation requires T cell receptor (TCR) recognition of foreign antigen peptides presented by major histocompatibility complexes (pMHC) on antigen presenting cells (APCs). Recent advances reveal that the TCR acts as a mechanoreceptor, but it remains unclear how pMHC/TCR engagement generates mechanical forces that are converted to intracellular signals. Here we propose a TCR Bending Mechanosignal (TBM) model, in which local bending of the T cell membrane on the nanometer scale allows sustained contact of relatively small pMHC/TCR complexes interspersed among large surface receptors and adhesion molecules on the opposing surfaces of T cells and APCs. Localized T cell membrane bending is suggested to increase accessibility of TCR signaling domains to phosphorylation, facilitate selective recognition of agonists that form catch bonds, and reduce noise signals associated with slip bonds.