Study Reveals How Actin Waves Guide T Cell Responses

Each time the body faces a new pathogen, the adaptive immune system launches a targeted defense. T cells, key players in this system, identify infected cells and direct their destruction. These cells constantly reshape themselves as they interact with other immune components. When a naive T cell comes into contact with an antigen presenting cell (APC), the two form a specialized interface called the immunological synapse. “The first few minutes of this contact are extremely important … they change the T cell forever,” says Sudha Kumari, senior author of a new study published in EMBO Reports.

Kumari’s team from the Indian Institute of Science examined how cytoskeletal behavior shapes this critical interaction. Their study identifies new patterns of actin dynamics that influence T cell signaling and receptor recycling.

Traditional models, based on conventional imaging, proposed that antigen-engaged T cell receptors (TCRs) cluster at the synapse and move inward toward its center, assisted by retrograde actin flow, before being internalized through endocytosis. But this explanation posed a puzzle—T cells can sequentially bind to multiple APCs, which would be inefficient if every receptor were internalized and resynthesized after each encounter.

To explore this, the IISc researchers used high-resolution live-cell imaging and designed an algorithm to trace individual TCR microclusters as they moved across an APC-like surface. They found that about 40% of the microclusters did not move toward the center but drifted outward to the cell’s edge, challenging the established model. The team discovered that actin was not only flowing inward but also forming outward-moving wavefronts—ripples that originated near the synapse center and spread toward the periphery. These waves appeared to carry TCR clusters outward, preventing their endocytosis. In T cells lacking the cytoskeletal protein WASP, often linked to immunodeficiency disorders, the coordination between actin waves and receptor motion was disrupted, reinforcing the connection between the two processes.

This dual flow of actin, moving both inward and outward, reveals a previously overlooked mechanism for maintaining receptor availability. “It’s like saying the river flows both ways. How do you even imagine that?” remarks Kumari.

According to co-author Samuel Khiangtze, “The remarkable patterns observed in the experiment raise a lot of interesting questions about the underlying physics of active cytoskeleton and motivate us to investigate the role of activity in the context of dynamic pattern formation.”