Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex

Elife. 2020 Jul 27;9:e55995. doi: 10.7554/eLife.55995.

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 antigen-presenting cell. 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.

Keywords: actin; cell biology; costimulation; cytoskeleton; immunology; inflammation; maturation; mechanotransduction; mouse; signal transduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Dendritic Cells / physiology*
  • HEK293 Cells
  • Humans
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / physiology*