Centrosomal Association with Nuclear Invaginations: Implications for T Cell Activation

T cells, a key component of the adaptive immune system, are activated when receptors on their surface recognize and bind to pathogenic peptides on antigen-presenting cells (APCs). T cell activation is a dynamic process resulting in dramatic changes to cellular morphology. The centrosome (the microtubule organizing center) migrates towards the immune synapse, the contact region between the T cell and the APC, upon activation. There, the centrosome plays a critical role in establishing cell polarity and directing intracellular transport mechanisms. We have observed that the centrosome maintains a close association with the nucleus throughout the activation process. Using confocal microscopy to study T cells activated on a planar glass surface, we have developed an analysis platform to generate 3D reconstructions of nuclei and characterize the geometry of the nuclear surface. We find that, as the nucleus spreads out and the centrosome migrates towards the synapse upon activation, the centrosome is consistently situated close to a deep invagination of the nucleus. Furthermore, we provide evidence that nuclear invaginations in activated T cells tend to be associated with less condensed chromatin, suggesting that the formation of invaginations may have implications for gene expression.