Synthetic α-Mannosyl Ceramide as a Potent Stimulant for an NKT Cell Repertoire Bearing the Invariant Vα19-Jα26 TCR α Chain Original Research Article

A NKT cell repertoire is characterized by the expression of the Vα19-Jα26 invariant TCR α chain (Vα19 NKT cell). This repertoire, as well as a well-established Vα14-Jα281 invariant TCR α+ NKT cell subset (Vα14 NKT cell), has been suggested to have important roles in the regulation of the immune system and, thus, is a major therapeutic target. Here, we attempted to find specific antigens for Vα19 NKT cells. Vα19 as well as Vα14 NKT cells exhibited reactivity to α-galactosyl ceramide (α-GalCer). Thus, a series of monoglycosyl ceramides with an axially oriented glycosidic linkage between the sugar and ceramide moiety were synthesized and their antigenicity to Vα19 NKT cells was determined by measuring their immune responses in culture with glycolipids. Comprehensive examinations revealed substantial antigenic activity for Vα19 NKT cells by α-mannosyl ceramide.