Open AccessUncovering a novel role of PLCβ4 in selectively mediating TCR signaling in CD8+ but not CD4+ T cells
Author(s) -
Miwa Sasai,
Ji Guo Su,
Masaaki Okamoto,
Kazumi Nishino,
Hikaru Nagaoka,
Eizo Takashima,
Ariel Pradipta,
Youngae Lee,
Hidetaka Kosako,
PannGhill Suh,
Masahiro Yamamoto
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20201763
Subject(s) - t cell receptor , microbiology and biotechnology , cd8 , cytotoxic t cell , biology , t cell , signal transduction , immune system , immunology , biochemistry , in vitro
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 CD8α ignites another cardinal signaling cascade involving phospholipase C β4 (PLCβ4). TCR-mediated responses were severely impaired in PLCβ4-deficient CD8+ T cells, whereas those in CD4+ T cells were intact. PLCβ4-deficient CD8+ T cells showed perturbed activation of peripheral TCR signaling pathways downstream of IP3 generation. Binding of PLCβ4 to the cytoplasmic tail of CD8α was important for CD8+ T cell activation. Furthermore, GNAQ interacted with PLCβ4, mediated double phosphorylation on threonine 886 and serine 890 positions of PLCβ4, and activated CD8+ T cells in a PLCβ4-dependent fashion. PLCβ4-deficient mice exhibited defective antiparasitic host defense and antitumor immune responses. Altogether, PLCβ4 differentiates TCR signaling in CD4+ and CD8+ T cells and selectively promotes CD8+ T cell–dependent adaptive immunity.