Abstract
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.