Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex
- The Children's Hospital of Philadelphia Research Institute, United States
- Children's Hospital of Philadelphia Research Institute, United States
Abstract
T cell activation by dendritic cells (DCs) involves forces exerted by the T cell actin cytoskeleton, which are opposed by the cortical cytoskeleton of the interacting APC. During an immune response, DCs undergo a maturation process that optimizes their ability to efficiently prime naïve T cells. Using atomic force microscopy, we find that during maturation, DC cortical stiffness increases via a process that involves actin polymerization. Using stimulatory hydrogels and DCs expressing mutant cytoskeletal proteins, we find that increasing stiffness lowers the agonist dose needed for T cell activation. CD4+ T cells exhibit much more profound stiffness-dependency than CD8+ T cells. Finally, stiffness responses are most robust when T cells are stimulated with pMHC rather than anti-CD3ε, consistent with a mechanosensing mechanism involving receptor deformation. Taken together, our data reveal that maturation-associated cytoskeletal changes alter the biophysical properties of DCs, providing mechanical cues that costimulate T cell activation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Institute of General Medical Sciences (GM104867)
- Janis K Burkhardt
National Institute of Allergy and Infectious Diseases (AI32828)
- Janis K Burkhardt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All studies, breeding and maintenance of animals was performed under AnimalCare and Use Protocol #667, as approved by The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee.
Copyright
© 2020, Blumenthal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex
eLife 9:e55995.
https://doi.org/10.7554/eLife.55995
