# Actin waves guide an outward movement of microclusters in the lymphocyte immunological synapse

## TL;DR

T cells use outward-moving actin waves to guide receptor clusters away from the central area, revealing a new mechanism for immune response regulation.

## Contribution

Discovery of anterograde actin waves as a novel mechanism for TCR microcluster movement in the immunological synapse.

## Key findings

- Antigen-engaged microclusters move outward via anterograde actin waves.
- Wiskott-Aldrich Syndrome Protein links TCR to anterograde actin waves.
- Jurkat T cells lack anterograde TCR migration and actin waves.

## Abstract

The lymphocyte immune response begins with antigen recognition on antigen-presenting cells, leading to the formation of the immunological synapse—a specialized interface for biochemical and biophysical exchange. At the synapse, most antigen-engaged receptor microclusters move inward toward the central supramolecular activation cluster (cSMAC) via retrograde F-actin flow, eventually clearing from the cell surface. This retrograde movement and receptor downregulation maintain antigen receptor homeostasis, critical for adaptive immunity, though its regulation remains unclear. Using live T cells, we identify a significant pool of antigen-engaged microclusters moving anterogradely toward the cell periphery, rather than the cSMAC. This movement is driven by actin waves propagating outward and coupling to microclusters through the Wiskott-Aldrich Syndrome Protein. These findings reveal a previously unrecognized mode of actin dynamics—anterograde actin waves—that co-exist with retrograde flow and direct microclusters away from the downregulation zone. This dual actin behavior underscores the complex cytoskeletal mechanisms T cells employ to regulate receptor distribution and maintain signaling homeostasis during immune activation.

The interplay of highly specialized actin dynamics—comprising retrograde flow and actin waves—with TCR microclusters at the immunological synapse, regulates receptor homeostasis during T-cell activation.

TCR translocates outwards, away from the central downregulation zone, in the primary T cell synapse.Anterograde actin waves guide outward TCR migration.Wiskott-Aldrich Syndrome Protein links TCR to anterograde actin waves.Both anterograde TCR migration and actin waves are missing in Jurkat T cells.

TCR translocates outwards, away from the central downregulation zone, in the primary T cell synapse.

Anterograde actin waves guide outward TCR migration.

Wiskott-Aldrich Syndrome Protein links TCR to anterograde actin waves.

Both anterograde TCR migration and actin waves are missing in Jurkat T cells.

The interplay of highly specialized actin dynamics—comprising retrograde flow and actin waves—with TCR microclusters at the immunological synapse, regulates receptor homeostasis during T-cell activation.