Monomeric C-reactive protein evokes TCR Signaling-dependent bystander activation of CD4+ T cells. (May 2023)

• Record Type: Journal Article
• Authors: Zhou, Liang; Chen, Sheng-Juan; Chang, Yue; Liu, Shan-Hui; Zhou, Yu-Fei; Huang, Xiao-Ping; Hua, Yu-Xin; An, Hao; Zhang, Shu-Hao; Melnikov, Ivan; Gabbasov, Zufar A.; Wu, Yi; Ji, Shang-Rong
• Is Part Of: Molecular immunology. Volume 157(2023)
• Page Start: 158
• Page End: 166
• Publication Date: 2023-05
• Subjects: C-reactive protein -- Pattern-recognition receptor -- T cell receptor -- Cholesterol -- Bystander T cell activation; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2023.03.025
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: Bystander activation of T cells is defined as induction of effector responses by innate cytokines in the absence of cognate antigens and independent of T cell receptor (TCR) signaling. Here we show that C-reactive protein (CRP), a soluble pattern-recognition receptor assembled noncovalently by five identical subunits, can instead trigger bystander activation of CD4 + T cells by evoking allosteric activation and spontaneous signaling of TCR in the absence of cognate antigens. The actions of CRP depend on pattern ligand-binding induced conformational changes that result in the generation of monomeric CRP (mCRP). mCRP binds cholesterol in plasma membranes of CD4 + T cells, thereby shifting the conformational equilibrium of TCR to the cholesterol-unbound, primed state. The spontaneous signaling of primed TCR leads to productive effector responses manifested by upregulation of surface activation markers and release of IFN-γ. Our results thus identify a novel mode of bystander T cell activation triggered by allosteric TCR signaling, and reveal an interesting paradigm wherein innate immune recognition of CRP transforms it to a direct activator that evokes immediate adaptive immune responses. Highlights: A novel mode of bystander activation in CD4+ T cells is identified. This mode depends on spontaneous signaling of TCR triggered by mCRP. mCRP acts via binging to membrane cholesterol to shift the conformational equilibrium of TCR.