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

The invariant natural killer T (iNKT) cell T cell receptor (TCR) is a specialized antigen receptor that recognizes glycolipid antigens presented by the MHC class I-like molecule, CD1d (Borg et al., 2007, Nature). Unlike conventional T cells that recognize peptide-MHC complexes, iNKT cells express a highly conserved TCR α-chain (Vα24-Jα18 in humans) paired with a limited range of β-chains (Brennan et al., 2013, Nature Reviews Immunology). Upon recognition of ligands such as KRN7000 (alpha-galactosylceramide), the iNKT TCR triggers rapid and robust secretion of both Th1 and Th2 cytokines, effectively bridging the innate and adaptive immune systems (Kawano et al., 1997, Science). This activation leads to the downstream recruitment of natural killer (NK) cells, dendritic cells, and cytotoxic T lymphocytes, making it a potent target for cancer immunotherapy (Giaccone et al., 2002, Clinical Cancer Research). In addition to oncology, the iNKT TCR is investigated for its role in modulating autoimmune diseases, asthma, and infectious diseases (Van Kaer et al., 2013, Frontiers in Immunology). Therapeutic strategies often involve using synthetic glycolipid agonists to stimulate iNKT cells, though challenges include potential iNKT cell anergy and the risk of systemic cytokine release syndrome (Exley et al., 2017, Cancer Immunology, Immunotherapy).

Other names

Vα24-Jα18 TCRVα14-Jα18 TCRiNKT receptorType I NKT cell receptorInvariant NKT cell receptor

Agonist binding to the iNKT TCR via the CD1d-glycolipid complex induces rapid activation and expansion of iNKT cells, leading to the secretion of diverse cytokines that modulate the broader immune environment (Kawano et al., 1997, Science).