T cells are immune cells that are key for the defense against pathogens and cancer. T cells depend on the membrane protein CD45 to initiate T cell receptor signaling, but how CD45 is controlled at the molecular level is poorly understood.
Vera Dunlock et al. (Dept. Tumor Immunology, research team of Annemiek van Spriel) discovered that CD45 is tightly controlled by tetraspanin protein CD53 at the cell surface of T cells. Using a combination of genetic experiments, advanced microscopy, and in vivo models, they demonstrate that CD53 is a key regulator of CD45 activity required for T cell immunity. T cells lacking CD53 were defective in cell division, interferon production and tumor rejection. These findings reveal a novel mechanism for the regulation of T cell signaling that provides valuable insight into T cell biology and immunological memory formation. This has import consequences for understanding immunity to cancer and infectious diseases.
Vera-Marie E. Dunlock, Abbey B. Arp, Simar Pal Singh, Stéphanie Charrin, Viet Nguyen, Erik Jansen, Fleur Schaper, Martin Ter Beest, Malou Zuidscherwoude, Sjoerd J. van Deventer, Britt Nakken, Peter Szodoray, Maria C. Demaria, Mark D. Wright, Laia Querol Cano, Eric Rubinstein, Annemiek B. van Spriel.