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Cell. 2014 Apr 10;157(2):357-368. doi: 10.1016/j.cell.2014.02.053.

Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling.

Author information

1
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
2
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
3
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.

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.

PMID:
24725404
PMCID:
PMC4123688
DOI:
10.1016/j.cell.2014.02.053
[Indexed for MEDLINE]
Free PMC Article

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