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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.

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In this study, the authors reported that increasing stiffness lowers the agonist dose needed for T cell activation by using the 96 well plates coated with polyacrylamide hydrogels spanning a stiffness range of 2–25 kPa.
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DOI:

10.7554/eLife.55995[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_separator color=”custom” border_width=”2″ accent_color=”#004a80″][/vc_column][/vc_row]