title: Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling.
abstract: TCR-pMHC interactions initiate adaptive immune responses, but the mechanism of how such interactions under force induce T cell signaling is unclear. We show that force prolongs lifetimes of single TCR-pMHC bonds for agonists (catch bonds) but shortens those for antagonists (slip bonds). Both magnitude and duration of force are important, as the highest Ca(2+) responses were induced by 10 pN via both pMHC catch bonds whose lifetime peaks at this force and anti-TCR slip bonds whose maximum lifetime occurs at 0 pN. High Ca(2+) levels require early and rapid accumulation of bond lifetimes, whereas short-lived bonds that slow early accumulation of lifetimes correspond to low Ca(2+) responses. Our data support a model in which force on the TCR induces signaling events depending on its magnitude, duration, frequency, and timing, such that agonists form catch bonds that trigger the T cell digitally, whereas antagonists form slip bonds that fail to activate.
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Liu
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Evavold
authors.affiliation: Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: cheng.zhu@bme.gatech.edu.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells; D002118:Calcium / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D011948:Receptors, Antigen, T-Cell; D002118:Calcium
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