4′-deoxy α-GalCer

αβ T cells can be activated by peptides, metabolites and lipids when bound to their requisite antigen (Ag)-presenting molecules. The CD1 family of MHC-class I-like molecules present an array of endogenous and foreign lipids Ags that are recognized by specialized T-cell populations. For example, NKT cells are activated by lipid-based Ags presented by CD1d. Based on ligand specificity and αβ TCR composition, NKT cells are broadly sub-divided into two populations, type I and II. α-Galactosylceramide (α-GalCer) is the prototypical Ag for type I NKT cells, which express an invariant TCR α-chain (TRAV10+TRAJ18+ (Vα24-Jα18) in humans and the orthologous TRAV11+TRAJ18+ (Vα14-Jα18) in mice). While type II NKT cells display a diverse TCR repertoire, and while their Ag-specificity remains unclear, they are nevertheless characterized as being non-reactive towards α-GalCer. The apparent functional divergence between type I and type II NKT cells arises, in part, from the interaction between the NKT TCR and CD1d–Ag.