Multiple clustered centrosomes in antigen-presenting cells foster T cell activation without MTOC polarization

Abstract

AbstractCellular polarization plays a pivotal role in regulating immunological processes and is often associated with centrosome reorientation. During immune synapse (IS) formation centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells (APCs) such as dendritic cells (DCs) amplify centrioles during maturation leading to increased centrosome numbers upon immune activation. How centrosome amplification in DCs affects IS formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that centrosome amplification in DCs enhances antigen-specific T cell activation. Extra centrioles in DCs form active centrosomes, which cluster during DC-T cell interactions and unlike in T cells, localize close to the cell center. Perturbing either centriole numbers or centrosome configuration in DCs results in impaired T cell activation. Collectively, our results highlight a crucial role for centrosome amplification and optimal centrosome positioning in APCs for controlling T cell responses.