Editors' ChoiceTCR Signaling

Uses the Force

Science Signaling  25 May 2010:
Vol. 3, Issue 123, pp. ec155
DOI: 10.1126/scisignal.3123ec155

The T cell receptor (TCR) is activated by antigenic peptide presented to it by the major histocompatibility complex (MHC) on the surface of an antigen-presenting cell (APC). Engagement of the TCR triggers the phosphorylation of tyrosine residues in associated CD3 subunits, which results in the activation of adaptor proteins and signaling molecules, such as intracellular Ca2+, that lead to T cell activation. Noting that previous studies have suggested that mechanical forces may play a role in regulating TCR responses, Li et al. investigated whether the TCR was sensitive to mechanical stimulation. The authors generated artificial APCs that had a stimulatory antibody against CD3 (CD3L) on their surface, using spacer molecules to generate CD3Ls of varying lengths. Although T cells bound to APCs with either short or long CD3Ls, only those APCs with short CD3Ls could activate the T cells, as assessed by measurement of intracellular Ca2+ by fluorescence microscopy. However, by applying a mild, perpendicular shear force through a micropipette, the authors generated Ca2+ responses in T cells bound to APCs with long CD3Ls. Applying shear stress to T cells bound to APCs or coverslips through antibodies against receptors other than the TCR did not generate Ca2+ flux. T cells that were bound to APCs with long CD3Ls also exhibited Ca2+ responses when they were physically pulled away from the APCs by a micropipette. Together, these data suggest that T cells can respond to physical forces through the TCR by initiating signaling.

Y.-C. Li, B.-M. Chen, P.-C. Wu, T.-L. Cheng, L.-S. Kao, M.-H. Tao, A. Lieber, S. R. Roffler, Cutting edge: Mechanical forces acting on T cells immobilized via the TCR complex can trigger TCR signaling. J. Immunol. 184, 5959–5963 (2010). [PubMed]