Invariant Natural Killer T cell T-cell Receptor (iNKT TCR) (iNKT TCR)

The Invariant Natural Killer T cell T-cell Receptor (iNKT TCR) is a specialized antigen receptor expressed on a unique subset of T cells that bridge the innate and adaptive immune systems (PMID: 17291281). Unlike conventional T-cell receptors that recognize peptide antigens presented by MHC molecules, the iNKT TCR specifically recognizes lipid and glycolipid antigens presented by the non-polymorphic MHC class I-like molecule, CD1d (PMID: 24510453). In humans, this receptor is characterized by a highly conserved invariant alpha chain (Vα24-Jα18) paired with a limited repertoire of beta chains, predominantly Vβ11 (UniProt). Upon activation by potent agonists such as alpha-galactosylceramide, the iNKT TCR triggers the rapid and robust secretion of a wide array of Th1 and Th2 cytokines, including interferon-gamma and interleukin-4. This rapid response allows iNKT cells to orchestrate the activity of various other immune cells, such as natural killer cells and cytotoxic T lymphocytes. Consequently, the iNKT TCR is a significant therapeutic target for enhancing anti-tumor immunity in oncology or modulating immune tolerance in autoimmune and inflammatory diseases (PMID: 28930661).

Other names

Type I NKT cell receptorVα24-Jα18/Vβ11 TCRSemi-invariant T-cell receptorCD1d-restricted T-cell receptorInvariant TCR

Agonist binding to the iNKT TCR in the context of CD1d presentation triggers rapid activation of iNKT cells, leading to the secretion of diverse cytokines (e.g., IFN-γ, IL-4) and subsequent activation of other immune cells like NK cells and dendritic cells (PMID: 24510453).