Centrosome Repositioning and Nuclear Architecture: Implications for T Cell Activation

T cells, crucial players in the adaptive immune response, are activated when receptors on their surface recognize and bind to pathogenic peptides on antigen-presenting cells (APCs). Activation triggers a series of changes in cellular morphology, including cytoskeletal reorganization and alterations to nuclear shape and chromatin organization. Upon activation, the centrosome (the microtubule organizing center) repositions toward the immune synapse, the contact site between the T cell and the APC, where it plays a critical role in establishing cell polarity and directing intracellular transport mechanisms. We find that in both human Jurkat T cells and in primary murine cytotoxic T lymphocytes, the centrosome remains tightly associated with a deep invagination of the nucleus. Upon activation, the centrosome and nuclear invagination reorient as a cohesive structural unit towards the synapse. This dynamic association is maintained by a balance of forces generated by the actin and microtubule cytoskeletons and motors. The intermediate filament vimentin is also enriched near the centrosome. Furthermore, this centrosome-proximal region of the nucleus constitutes a distinctive chromatin microenvironment, raising implications for activation driven gene expression. These findings deepen our understanding of nuclear organization and dynamics during T cell activation and establish a foundation for examining how nuclear architecture and interactions with the centrosome regulate immune function.