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

eLife

Daniel Blumenthal¹  Lyndsay Avery¹  Vidhi Chandra¹  Janis K Burkhardt¹ 

[1] Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States;

关键词: mechanotransduction;    maturation;    signal transduction;    actin;    cytoskeleton;    costimulation;   

DOI  :  10.7554/eLife.55995

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown