| First Author | Sasai M | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 7 | PubMed ID | 33970189 |
| Mgi Jnum | J:343893 | Mgi Id | MGI:6724857 |
| Doi | 10.1084/jem.20201763 | Citation | Sasai M, et al. (2021) Uncovering a novel role of PLCbeta4 in selectively mediating TCR signaling in CD8+ but not CD4+ T cells. J Exp Med 218(7) |
| abstractText | Because of their common signaling molecules, the main T cell receptor (TCR) signaling cascades in CD4+ and CD8+ T cells are considered qualitatively identical. Herein, we show that TCR signaling in CD8+ T cells is qualitatively different from that in CD4+ T cells, since CD8alpha ignites another cardinal signaling cascade involving phospholipase C beta4 (PLCbeta4). TCR-mediated responses were severely impaired in PLCbeta4-deficient CD8+ T cells, whereas those in CD4+ T cells were intact. PLCbeta4-deficient CD8+ T cells showed perturbed activation of peripheral TCR signaling pathways downstream of IP3 generation. Binding of PLCbeta4 to the cytoplasmic tail of CD8alpha was important for CD8+ T cell activation. Furthermore, GNAQ interacted with PLCbeta4, mediated double phosphorylation on threonine 886 and serine 890 positions of PLCbeta4, and activated CD8+ T cells in a PLCbeta4-dependent fashion. PLCbeta4-deficient mice exhibited defective antiparasitic host defense and antitumor immune responses. Altogether, PLCbeta4 differentiates TCR signaling in CD4+ and CD8+ T cells and selectively promotes CD8+ T cell-dependent adaptive immunity. |
