Abstract
T cells are activated by target cells via an intimate contact, termed immunological synapse (IS). Cellular mechanical properties, especially stiffness, are essential to regulate cell functions. However, T cell stiffness at a subcellular level at the IS still remains largely elusive. In this work, we established an atomic force microscopy (AFM)-based elasticity mapping method on whole T cells to obtain an overview of the stiffness with a resolution of ~60 nm. Using primary human CD4+ T cells, we show that when T cells form IS with stimulating antibody-coated surfaces, the lamellipodia are stiffer than the cell body. Upon IS formation, T cell stiffness is enhanced both at the lamellipodia and on the cell body. Chelation of intracellular Ca2+ abolishes IS-induced stiffening at the lamellipodia but has no influence on cell-body-stiffening, suggesting different regulatory mechanisms of IS-induced stiffening at the lamellipodia and the cell body.
Highlights
T cells belong to the adaptive immune system and can be classified into CD4+ T cells and CD8+ T cells
This morphology of lamellipodia detected by atomic force microscopy (AFM) resembles what have been observed from scanning electron microscopy and immunostaining (Saitakis, Dogniaux et al, 2017, Schoppmeyer, Zhao et al, 2017)
We postulated that perturbation of cytoskeleton would significantly influence T cell stiffening induced by immunological synapse (IS) formation both at the lamellipodia and the cell body
Summary
T cells belong to the adaptive immune system and can be classified into CD4+ T cells and CD8+ T cells. CD4+ T cells are essential for orchestrating immune responses and CD8+ T cells are the key players to eliminate tumor and pathogen-infected cells. T cells are activated by the engagement of T-cell receptors (TCR) with the matching antigen. CD3 molecules, one key component of the TCR complex, transduce the signal to activate downstream pathways leading to formation of a tight junction between T cells and target cells termed the immunological synapse (IS). The adhesion molecule LFA-1 (lymphocyte function-associated antigen 1) binds its ligand on the target cells to seal and stabilize the IS. Ca2+ serves as an essential second messenger in T cells to regulate their key functions such as activation, proliferation, and effector functions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
