Full T-Cell Activation but not Early Signaling Requires Actin Remodeling

Abstract

T-cell activation is widely thought to rely on cytoskeletal remodeling at all stages. Using super-resolution optical STED and lattice-light-sheet microscopy we show that during activation T cells sequentially rearrange their cortical actin using two networks of different-length F-actins creating three distinct structures. A cortical actin ring formed at the initial contact interface evolves into a rosette-shaped structure comprising a coarse central fiber network and flat lamellipodium as the cell spreads. The formation of actin “spikes” extending to the contact edge then marks a contraction phase leading to immunological synapse formation. We also show, however, that the earliest steps in T-cell signaling require remarkably little contact with activating surfaces and no cytoskeletal rearrangements. Blocking actin remodeling pharmacologically produces more rather than less early signaling. Our work shows that whereas a complex program of cytoskeletal reorganization is initiated by T-cell activation, early signaling occurs entirely independently of cytoskeletal remodeling.