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Invariant natural killer T cell receptor (via CD1d) (iNKT cell TCR)

Target
iNKT cell TCR
Molecular classification
T cell receptor (TCR), Receptor, Immunoglobulin superfamily member
01

Overview

The invariant natural killer T cell receptor (iNKT TCR) refers to a semi-invariant αβ T cell receptor expressed by invariant natural killer T cells, whose defining feature is their recognition of glycolipid antigens presented by the non-classical MHC class I-like molecule CD1d. Unique among TCRs, the iNKT cell TCR α chain uses a near-invariant Vα–Jα rearrangement (Vα24-Jα18 in humans; Vα14-Jα18 in mice), paired with a limited Vβ chain. This configuration allows iNKT cells to recognize a limited, but immunologically significant, repertoire of self and foreign glycolipids, enabling them to respond rapidly and robustly by secreting large amounts of cytokines. CD1d presentation of glycolipids such as α-galactosylceramide leads to immediate activation of iNKT cells, which are important for both antimicrobial defense and immune regulation. Aberrant activation or regulation of this axis has been implicated in infection, inflammation, cancer, and autoimmune disease[1][2][3][4][9]. Note: The "via CD1d" qualifier is essential: iNKT cells are specifically defined by their recognition of glycolipid antigens in the context of CD1d, and not MHC-peptide complexes[2][3][4][9]. The term "invariant natural killer T cell receptor via CD1d" is scientifically accurate and describes a well-recognized immune receptor system.

Other names
iNKT TCRinvariant NKT cell TCRtype I NKT cell receptorsemi-invariant TCR (for NKT cells)Vα14-Jα18 TCR (mouse)Vα24-Jα18 TCR (human)
02

Mechanism of action

Activation of iNKT cells via TCR engagement by glycolipids presented on CD1d, leading to rapid cytokine production and modulation of immune responses[1][4][9].

03

Biological functions

Antigen recognition (specifically glycolipid antigens)Immune response modulationCytokine secretion (rapid release of interferon-γ, interleukin-4, etc.)Bridging innate and adaptive immunity
04

Disease associations

InfectionInflammationCancerAutoimmunity (context-dependent)Other (immune regulation in metabolic and hepatic diseases)
05

Safety considerations

Overactivation may trigger pathogenic inflammation or exacerbate autoimmune disease[9]Non-specific immune activation risksCytokine storm if excessively stimulated
06

Interacting drugs

α-galactosylceramide (α-GalCer)

2 more in the full profile.

07

Biomarkers

iNKT cell frequency or activation status (by staining for iNKT TCR with CD1d-tetramer loaded with α-GalCer)Serum cytokine levels (e.g., IFNγ, IL-4) post-activationCD1d expression on antigen-presenting cells

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