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Force Generation upon T Cell Receptor Engagement

By Julien Husson, Karine Chemin, Armelle Bohineust, Claire Hivroz and Nelly Henry


T cells are major players of adaptive immune response in mammals. Recognition of an antigenic peptide in association with the major histocompatibility complex at the surface of an antigen presenting cell (APC) is a specific and sensitive process whose mechanism is not fully understood. The potential contribution of mechanical forces in the T cell activation process is increasingly debated, although these forces are scarcely defined and hold only limited experimental evidence. In this work, we have implemented a biomembrane force probe (BFP) setup and a model APC to explore the nature and the characteristics of the mechanical forces potentially generated upon engagement of the T cell receptor (TCR) and/or lymphocyte function-associated antigen-1 (LFA-1). We show that upon contact with a model APC coated with antibodies towards TCR-CD3, after a short latency, the T cell developed a timed sequence of pushing and pulling forces against its target. These processes were defined by their initial constant growth velocity and loading rate (force increase per unit of time). LFA-1 engagement together with TCR-CD3 reduced the growing speed during the pushing phase without triggering the same mechanical behavior when engaged alone. Intracellular Ca2+ concentration ([Ca2+]i) was monitored simultaneously to verify the cell commitment in the activation process. [Ca2+]i increased a few tens of seconds after the beginning of the pushing phase although no strong correlation appeared between the two events. The pushing phase was driven by actin polymerization. Tuning the BFP mechanical properties, we could show that the loading rate during the pulling phase increased with the target stiffness. This indicated that a mechanosensing mechanism is implemented in the early steps of the activation process. We provide here the first quantified description of force generation sequence upon local bidimensional engagement of TCR-CD3 and discuss its potential role in a T cell mechanically-regulated activation process

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  26. (1998). Micropipet-based pico force transducer: in depth analysis and experimental verification.
  27. (1978). Models for the specific adhesion of cells to cells.
  28. (2007). Molecular mechanisms involved in T cell receptor triggering.
  29. (1996). Polarity of T cell shape, motility, and sensitivity to antigen.
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  32. (2007). Regulation of T-cell activation by the cytoskeleton.
  33. (2007). Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates.
  34. (1995). Sensitive force technique to probe molecular adhesion and structural linkages at biological interfaces.
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  37. (2009). Spatiotemporal analysis of cell response to a rigidity gradient: a quantitative study using multiple optical tweezers.
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  39. (2001). Synaptic pattern formation during cellular recognition.
  40. (1993). Synchrony of cell spreading and contraction force as phagocytes engulf large pathogens.
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  42. (2006). T cells like a firm molecular handshake.
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  44. (1999). TCR, LFA-1, and CD28 play unique and complementary roles in signaling T cell cytoskeletal reorganization.
  45. (2009). The alphabeta T cell receptor is an anisotropic mechanosensor.
  46. (2003). The diversity of immunological synapses.
  47. (2009). The hard life of soft cells.
  48. (1999). The immunological synapse: a molecular machine controlling T cell activation.
  49. (2008). The receptor deformation model of TCR triggering.
  50. (2001). The TCR triggering puzzle.
  51. (2002). Two-photon imaging of lymphocyte motility and antigen response in intact lymph node.