BENGALURU: A new study from the Indian Institute of Science (IISc) has uncovered how dynamic movements of actin, a structural protein inside cells, help T cells sustain immune responses by preserving critical surface receptors during early contact with infected cells.T cells are central to adaptive immunity, the arm of the immune system that recognises and eliminates specific pathogens. As per the study, when a naive T cell encounters an antigen-presenting cell (APC), it forms a specialised contact zone called the immunological synapse. Events in the first few minutes of this interaction determine how the T cell will respond.Previous studies had shown that antigen-bound T cell receptors (TCRs) cluster at the synapse and move towards its centre, driven by the backward flow of actin filaments. This inward movement was thought to prepare the receptors for endocytosis, allowing the T cell to disengage from the APC. However, this posed a puzzle: T cells are known to interact with multiple APCs in succession, something that would be difficult if most receptors were internalised and had to be newly produced each time.To investigate this, a team led by Sudha Kumari from the Department of Microbiology and Cell Biology, working with Sumantra Sarkar’s group from the Department of Physics, used high spatial and temporal resolution imaging to track TCR movement during contact with an APC-like surface. They also developed a tracking algorithm to analyse the trajectories of individual receptor clusters.The results, published in the journal “EMBO Reports”, showed that nearly 40% of TCR microclusters moved away from the centre of the immunological synapse towards the cell periphery, a behaviour that could not be explained by actin’s conventional inward flow alone.The researchers found that actin was forming outward-propagating wavefronts around the synapse centre. These waves were tightly coupled to the outward motion of TCR microclusters, effectively rescuing them from endocytosis. Experiments with naive T cells lacking the protein WASP, which is associated with immunodeficiency disorders, showed a breakdown in this coupling, underlining the role of actin dynamics in the process, IISc said.“It’s like saying the river flows both ways,” Kumari said, referring to the paradoxical observation of actin-driven transport in opposing directions.The findings highlight a previously underappreciated layer of control at the immune synapse. According to first author Aheria Dey, a PhD student at IISc, this contact site is the T cell’s “decision-making point”, and small changes in cytoskeletal behaviour could influence whether immune responses are effective or faulty.The work also raises broader questions in biophysics about how active cellular materials generate complex patterns, with potential implications for understanding immune disorders, cancer immunotherapy, and autoimmune diseases.
