Assembly, expression, and signal transduction by the pre-T-cell receptor (pre-TCR) and TCR complexes are critical for normal thymocyte development. How environmental cues sensed by these two receptor complexes are translated into biological responses that result in the generation of functionally mature T cells is increasingly better understood. Invariant CD3gamma, delta, epsilon, and zeta polypeptides are central to the function of these two receptor complexes. CD3 chains ensure correct intracellular assembly, surface expression, and signal transduction via the receptors in ligand-independent and -dependent manners. In the present review, the roles of the CD3 chains, particularly CD3gamma, delta, and epsilon, in thymocyte differentiation in mice and humans are reviewed.
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http://dx.doi.org/10.1111/j.1600-065X.2009.00835.x | DOI Listing |
J Am Chem Soc
January 2025
State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Type 1 diabetes (T1D) is an autoimmune disorder in which pancreatic β-cells are destroyed by CD8 T cells. Anti-CD3 antibody effectively treats early-stage T1D when β-cell autoantibodies are detected but before symptoms appear. However, it impairs the immune system temporarily, exposing individuals to infection.
View Article and Find Full Text PDFSignal Transduct Target Ther
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi, China.
The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.
View Article and Find Full Text PDFImmune Netw
December 2024
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
Chimeric antigen receptor-transduced T (CAR-T) cell therapy is an effective cell therapy against advanced hematological tumors. However, the use of autologous T cells limits its timely and universal generation. Allogeneic CAR-T cell therapy may be a good alternative as a ready-to-use therapeutic.
View Article and Find Full Text PDFFront Immunol
January 2025
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Introduction: T cell activation requires T cell receptor (TCR) engagement by its specific ligand. This interaction initiates a series of proximal events including tyrosine phosphorylation of the CD3 and TCRζ chains, recruitment, and activation of the protein tyrosine kinases Lck and ZAP70, followed by recruitment of adapter and signaling proteins. CD28 co-stimulation is also required to generate a functional immune response.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Recombinant antibodies and, more recently, T cell receptor (TCR)-engineered T cell therapies represent two immunological strategies that have come to the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell-based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T cell), a chimeric antigen receptor (CAR) with the variable domains of a neoepitope-reactive TCR as a binding domain (TCR-CAR-T cell) or a TCR-like antibody as a binding domain (TCR-like CAR-T cell). Furthermore, the synthetic T cell receptor and antigen receptor (STAR) and heterodimeric TCR-like CAR (T-CAR) are designed as a double-chain TCRαβ-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-Cα and TCR-Cβ, respectively, resulting in TCR signaling.
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