Invariant natural killer T (iNKT) TCR Research Tool

Invariant natural killer T (iNKT) cells represent a unique subset of lymphocytes. They participate in the pathological processes of numerous distinct diseases and also play a role in maintaining homeostasis. For instance, these cells get activated when pathogens invade the body. They are also capable of inhibiting autoimmune disorders, as well as allograft rejection and graft-versus-host disease. Gaining a deeper comprehension of the varied roles of iNKT cells is essential for creating immunotherapeutic approaches that target this specific cell type.

RGBiotech provide the plasmid vector that can be used to establish a Jurkat-cell-based reporter system, to study the interaction between human iNKT-TCR and lipid antigen. RGBiotech also provide the plasmid vector that can be used for generating a cell line (like BW5147) that has a strong capacity to present lipid antigens (convenient, easy-to-use, lipid antigen presenting cells expressing human CD1D and CD80). The human iNKT-TCR reporter system, generated using our plasmid vectors, enables a shorter turnaround time and lower costs compared to traditional iNKT cell assays, and is applicable for screening potential new lipid antigens that influence human iNKT cell activation. For more information or inquiry, please contact us at admin@rgbiotech.com.

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Invariant natural killer T (iNKT) cells are a unique, evolutionarily conserved subset of innate-like lymphocytes. They express a semi-invariant T cell receptor (TCR) that recognizes glycolipid antigens presented by the non-classical major histocompatibility complex (MHC) class I-like molecule CD1d, distinguishing them from conventional T cells.

1. Introduction to iNKT TCR

1) Structural Features
a) Semi-invariant composition: iNKT TCRs consist of a highly conserved α-chain (Vα14-Jα18 in mice, Vα24-Jα18 in humans) paired with a limited repertoire of β-chains (e.g., Vβ8.2, Vβ7 in mice; Vβ11 in humans), unlike the diverse TCRs of conventional T cells.
b) CD1d-glycolipid recognition mode: The TCR α-chain directly interacts with the polar head group of the glycolipid antigen and the CD1d molecule, while the β-chain stabilizes the TCR-CD1d-antigen complex, ensuring specific recognition of glycolipids.

2) Functional Roles
a) Initiation of iNKT cell activation: Binding of iNKT TCR to CD1d-glycolipid complexes triggers intracellular signaling cascades, leading to rapid cytokine secretion and iNKT cell activation.
b) Determination of functional polarization: The specific β-chain of iNKT TCR can influence cytokine secretion profiles (e.g., Th1- or Th2-type cytokines), shaping the immune response direction.
c) Target for therapeutic engineering: Modifying iNKT TCRs (e.g., enhancing affinity for tumor-associated glycolipids) to redirect iNKT cells to recognize and eliminate tumor cells, a promising approach in cancer immunotherapy.

2. Functions of iNKT Cells

3. Differences Between iNKT Cells and Other T Cell Subsets

4. Research Hotspots and Challenges in iNKT Cell Studies

1) Research Hotspots
a) iNKT cells in cancer immunotherapy: Exploring strategies to activate iNKT cells (e.g., using α-galactosylceramide, α-GalCer) to enhance anti-tumor immunity, or engineering iNKT cells for adoptive cell therapy.
b) Role in metabolic diseases: Investigating how iNKT cells regulate insulin resistance, obesity-related inflammation, and non-alcoholic fatty liver disease (NAFLD) to develop metabolic disease treatments.
c) Development of iNKT cell-targeted vaccines: Designing glycolipid-based vaccines that activate iNKT cells to improve immune protection against pathogens like bacteria and viruses.

2) Research Challenges
a) Limited understanding of antigen specificity: The range of endogenous and exogenous glycolipid antigens recognized by iNKT cells remains unclear, hindering the development of targeted activators.
b) Tissue-specific functional heterogeneity: iNKT cells in different tissues (e.g., liver vs. adipose tissue) exhibit distinct phenotypes and functions, making it difficult to generalize therapeutic effects.
c) Tolerance and hyporesponsiveness: Long-term activation of iNKT cells can lead to hyporesponsiveness, reducing their therapeutic efficacy in chronic diseases.

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