T cell receptor on invariant natural killer T cell (iNKT TCR)

The T cell receptor on invariant natural killer T cell refers to the semi-invariant αβ T cell receptor (TCR) that is characteristic of type I/invariant natural killer T (iNKT) cells. This receptor consists of a highly conserved α-chain (Vα14-Jα18 in mice; Vα24-Jα18 in humans) paired with a limited set of β-chains (Vβ8.2, Vβ7, Vβ2 in mice, Vβ11 in humans). iNKT TCR specifically recognizes glycolipid antigens presented by the non-classical MHC class I-like molecule CD1d, with alpha-galactosylceramide (α-GalCer) being the prototypical antigen. Engagement of this TCR triggers rapid and robust cytokine production (e.g., IFN-γ, IL-4), enabling iNKT cells to bridge innate and adaptive immunity, and influence diverse processes such as infection clearance, anti-tumor immunity, autoimmunity, allergy, inflammation, and transplantation tolerance. The iNKT TCR is considered a therapeutic target because modulating its activity through agonistic ligands (like α-GalCer) or blockade can impact immune responses. The unique invariant nature of this TCR, its restriction to CD1d, and its non-peptide glycolipid antigen specificity distinguish it from conventional T cell receptors.

Other names

iNKT cell TCRinvariant NKT cell TCRType I NKT cell TCRVα14-Jα18 TCR (mouse)Vα24-Jα18 TCR (human)invariant natural killer T cell receptorNKT TCR

Agonism by glycolipid antigens (e.g., α-GalCer) presented by CD1d Stimulation leading to cytokine release and immune activation