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Abstract
Despite intensive investigation, the mechanisms of T cell receptor (TCR)-mediated signal generation remain poorly understood. Here we review various dynamic processes at the cell membrane that might critically control this signaling. Firstly, we summarize recent reports providing new information on the sensitivity of TCR/ligand interaction to the membrane environment and particularly to applied forces. Secondly, we review recent evidence that forces and displacements are continuously generated at cell surfaces. Thirdly, we summarize recent experimental evidence demonstrating the capacity of forces to generate signals. Lastly, we provide a quantitative model to exemplify the capacity of dynamic processes to modulate TCR properties such as specificity that were previously difficult to explain with conventional models. It is concluded that the described dynamic processes must be integrated into current models of TCR signaling.
Highlights
INTRODUCTIONThe mechanisms of T cell receptor (TCR)-mediated signal generation remains poorly understood
Despite intensive investigation, the mechanisms of T cell receptor (TCR)-mediated signal generation remains poorly understood
We provide a quantitative model to exemplify the capacity of dynamic processes to modulate TCR properties such as specificity that were previously difficult to explain with conventional models
Summary
The mechanisms of T cell receptor (TCR)-mediated signal generation remains poorly understood. Biomembrane force probes were introduced to dramatically improve the atomic force microscopes: the cantilever is replaced with a soft vesicle that acts as a tunable spring, increasing the dynamic range of measurements (Merkel et al, 1999) While these methods have yielded much information on interactions involving selectins, integrins, cadherins, and members of the immunoglobulin superfamily (Bongrand, 1999), it was only recently that the TCR/pMHC interaction was monitored at the single-molecule level (Huang et al, 2010; Huppa et al, 2010; Puech et al, 2011; Robert et al, 2012). Molecular contacts were observed with an accuracy of a few www.frontiersin.org
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