Protein 4.1R negatively regulates CD8⁺ T‐cell activation by modulating phosphorylation of linker for activation of T cells.

T cells; ERYTHROCYTES; INTERLEUKIN-2; MEMBRANE proteins; PHOSPHORYLATION

Summary: Protein 4.1R, an 80 000 MW membrane skeleton protein, is a vital component of the red blood cell membrane cytoskeleton that stabilizes the spectrin–actin network and regulates membrane properties of deformability and mechanical stability. It has been shown that 4.1R is expressed in T cells, including CD8+ T cells, but its role in CD8+ T cells remains unclear. Here, we have explored the role of 4.1R in CD8+ T cells using 4.1R−/− mice. Our results showed that cell activation, proliferation and secretion levels of interleukin‐2 and interferon‐γ were significantly increased in 4.1R−/− CD8+ T cells. Furthermore, the phosphorylation levels of linker for activation of T cells (LAT) and its downstream signaling molecule extracellular signal‐regulated kinase were enhanced in the absence of 4.1R. In vitro co‐immunoprecipitation experiments showed a direct interaction between 4.1R and LAT. Moreover, 4.1R−/− CD8+ T cells and mice exhibited an enhanced T‐cell‐dependent immune response. These data enabled the identification of a negative regulation function for 4.1R in CD8+ T cells by a direct association between 4.1R and LAT, possibly through inhibiting phosphorylation of LAT and then modulating intracellular signal transduction. [ABSTRACT FROM AUTHOR]