A recent study by the Indian Institute of Science (IISc) has shed light on how T cells, crucial components of the adaptive immune system, maintain sustained immune responses. The research reveals that the dynamic movement of actin, a structural protein within cells, plays a vital role in preserving critical surface receptors on T cells during their initial contact with infected cells.
T cells are essential for adaptive immunity, enabling the immune system to recognize and eliminate specific pathogens. When a naive T cell encounters an antigen-presenting cell (APC), a specialized contact zone known as the immunological synapse is formed. The events occurring within the first few minutes of this interaction determine the T cell's subsequent response.
Previous research indicated that antigen-bound T cell receptors (TCRs) cluster at the synapse and move towards its center, driven by the backward flow of actin filaments. This inward movement was initially thought to prepare the receptors for endocytosis, facilitating the T cell's detachment from the APC. However, this raised a question, as T cells are known to interact with multiple APCs sequentially, a process that would be challenging if most receptors were internalized and required constant regeneration.
To investigate this paradox, a team led by Sudha Kumari from the Department of Microbiology and Cell Biology, in collaboration with Sumantra Sarkar's group from the Department of Physics, employed high-resolution imaging to monitor TCR movement during contact with an APC-like surface. They also developed a tracking algorithm to analyze the trajectories of individual receptor clusters.
The findings, published in "EMBO Reports," demonstrated that nearly 40% of TCR microclusters moved away from the center of the immunological synapse towards the cell periphery, a behavior that couldn't be explained by the conventional inward flow of actin alone. The researchers discovered that actin was forming outward-propagating wavefronts around the synapse center. These waves facilitate the redistribution of TCRs, allowing the T cell to reuse these key receptors for subsequent interactions with other APCs.
These actin waves ensure that T cells can efficiently interact with multiple antigen-presenting cells without depleting their receptors. This mechanism is crucial for maintaining a robust and sustained immune response. The study provides a new understanding of the dynamic processes that govern T cell activation and receptor usage, highlighting the importance of actin dynamics in adaptive immunity. This research could potentially lead to new strategies for enhancing T cell function in immunotherapies and vaccines.
