| First Author | Fan D | Year | 2019 |
| Journal | Immunology | Volume | 157 |
| Issue | 4 | Pages | 312-321 |
| PubMed ID | 31135971 | Mgi Jnum | J:279081 |
| Mgi Id | MGI:6323797 | Doi | 10.1111/imm.13085 |
| Citation | Fan D, et al. (2019) Protein 4.1R negatively regulates CD8(+) T-cell activation by modulating phosphorylation of linker for activation of T cells. Immunology 157(4):312-321 |
| abstractText | 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-gamma 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. |
