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

Journal article

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.

Authors: Dey, A; Khiangte, SZ; Mandal, S; Colin-York, H; Fritzsche, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: EMBO Reports
• Volume: 27
• Issue: 4
• Pages: 834-852
• Publication date: 2025-12-22
• Acceptance date: 2025-12-04
• DOI: 10.1038/s44319-025-00676-2
• EISSN: 1469-3178
• ISSN: 1469-3178
• Language: English
• Keywords: Actin Retrograde Flow; T Cell Receptor Microcluster Dynamics; Immunological Synapse; Actin Waves; Wiskott-Aldrich Syndrome Protein