title: T cell activation requires force generation.
abstract: Triggering of the T cell receptor (TCR) integrates both binding kinetics and mechanical forces. To understand the contribution of the T cell cytoskeleton to these forces, we triggered T cells using a novel application of atomic force microscopy (AFM). We presented antigenic stimulation using the AFM cantilever while simultaneously imaging with optical microscopy and measuring forces on the cantilever. T cells respond forcefully to antigen after calcium flux. All forces and calcium responses were abrogated upon treatment with an F-actin inhibitor. When we emulated the forces of the T cell using the AFM cantilever, even these actin-inhibited T cells became activated. Purely mechanical stimulation was not sufficient; the exogenous forces had to couple through the TCR. These studies suggest a mechanical-chemical feedback loop in which TCR-triggered T cells generate forceful contacts with antigen-presenting cells to improve access to antigen.
authors.affiliation: Stanford Biophysics, Stanford University, Stanford, CA 94305.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Hu
authors.affiliation: Stanford Biophysics, Stanford University, Stanford, CA 94305 Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, Stanford University, Stanford, CA 94305 manish.butte@stanford.edu.
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Butte
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D008213:Lymphocyte Activation / Q000187:drug effects; D008822:Mice, Transgenic; D018625:Microscopy, Atomic Force; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000941:Antigens; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053778:Thiazolidines; C037067:latrunculin A; D002118:Calcium