2025/12/22 by Aheria Dey, Samuel Z Khiangte, Srishti Mandal +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · Immunology and Microbiology · #Cellular Mechanics and Interactions #Cell Adhesion Molecules Research #T-cell and B-cell Immunology
paper · pdf · doi:10.1038/s44319-025-00676-2
openalex created_date 2025/12/22 · openalex publication_date 2025/12/22 · openalex updated_date 2026/07/23
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.