| First Author | Blumenthal D | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32720892 | Mgi Jnum | J:294233 |
| Mgi Id | MGI:6455118 | Doi | 10.7554/eLife.55995 |
| Citation | Blumenthal D, et al. (2020) Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex. Elife 9:e55995 |
| abstractText | 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 naive 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-CD3epsilon, 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. |
