Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling

The RAG1 Ubiquitin Ligase Domain Enhances the Assembly and Selection of T Cell Receptor Genes to Restrain the Autoimmune Hazard of Generating T Cell Receptor Diversity

“…However, this study did not investigate the effects of TCR signaling strength on differentiation of iNKT precursor cells. Prior work that the development of NKT2 and NKT17 but not NKT1 cells is impaired by a hypomorphic mutation of the Zap70 TCR signaling protein that weakens TCR signaling supports the notion that strength of TCR signaling influences iNKT cell differentiation (40). Although TCRb amino acids encoded by Jb segments and CDR3b nucleotides influence ab TCR specifity of iNKT cells (41), it is hard to explain how the minor changes in Db and Jb usage in PG mice would substantially alter TCR signaling to impair the generation of iNKT subtypes from iNKT precursor cells.…”

“…How iNKT cell subsets develop from agonist-selected iNKT progenitor cells remains incompletely understood. A recent study in mice expressing αβ TCRs from a single pre-assembled Vα14- Jα18 rearrangement formulated a model that iNKT cell development is a two step process where the first step involves transient uniform TCR signaling that drives agonist selection of DP thymocytes into iNKT common precursors and the second step involves antigen/TCR-independent differentiation of different mature effector subset through differential gene expression (40). However, this study did not investigate the effects of TCR signaling strength on differentiation of iNKT precursor cells.…”

UGCG relieves iNKT cell-mediated liver injury by triggering endoplasmic reticulum stress in mice

“…iNKT cells are one of the main subsets of NKT cells that recognize glycosphingolipids presented by CD1d by expressing semi-invariant TCR. iNKT cells can be selectively enriched in the liver 30,31 and secrete a series of cytokines (including IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10) when activated by GSLs antigens, thereby participating in immune-mediated liver injury 14,32 . UGCG acts as the key enzyme that catalyzes the rst step in the biosynthesis of GSLs, and its activity directly affects the level of GSLs.…”

“…As the main undertaker of inheriting the function of NKT cells, invariant NKT (iNKT) cells can recognize the lipid antigens presented by CD1d, and after being activated, secrete a series of cytokines, thus participating in the regulation of innate and adaptive immunity 10,11,12 . A typical example is that iNKT cells are rapidly activated by the stimulation of α-galactosylceramide (α-GalCer) and secrete a large number of Th1 and Th2 cytokines to participate in the immune response 13,14 . In addition, iNKT cells can interact with other immune cells in a cell-to-cell manner to regulate host immunity 12 .…”

Temporal profiling of CD4 T-cell activation and differentiation upon SARS-CoV-2 spike protein immunisation

“…Using the fluorescent Timer protein (Timer), which spontaneously and irreversibly shifts its emission spectrum from blue fluorescence (Blue) to red fluorescence (Red), Tocky allows analysis of temporally dynamic changes of individual cells in vivo. Nr4a3-Tocky is a Timer reporter mouse line for the TCR signal downstream gene Nr4a3 , can be used to analyse antigen-reactive T-cell responses and differentiation ( 31-33 ) by showing temporal changes in T-cell activation and differentiation following TCR signals in vivo ( 34 ). Thus, in this study, we aimed to analyse S protein-induced polyclonal T-cell response using Nr4a3-Tocky and to understand antigen-dependent control of T-cell differentiation and the properties of S protein in relation to T-cell immunogenicity in vivo.…”