Non-reducing end α-mannosylated glycolipids as potent activators for invariant Vα19 TCR-bearing natural killer T cells Review Article

A novel invariant Vα19-Jα33 T cell receptor α chain, first found in mammalian blood cells, was primarily expressed by natural killer T cell repertoire (Vα19 NKT cell). Attempts have been made to find specific antigens for Vα19 NKT cells. A series of α- and β-glycosyl ceramides were synthesized and tested whether they had potential to stimulate the cells isolated from invariant Vα19-Jα33 TCR transgenic mice (where the development of Vα19 NKT cells is facilitated). Comprehensive examinations revealed substantial antigenic activity in α-ManCer that was presented by MR1, one of the MHC class Ib molecules. Next, naturally occurring and synthetic α-mannosyl glycolipids were further analyzed to determine structural requirements for natural ligands for Vα19 NKT cells. As a result, α-mannosyl phosphatidyl inositols (PI) such as (α-Man)2-PI and α-Man-α-GlcNH2-PI (a partial structure of mycobacterial lipoarabinomannan and GPI-anchors) as well as α-ManCer derivatives were found to activate Vα19 NKT cells in vivo and in vitro. Thus, Vα19 NKT cells are possibly responsive to certain α-mannosyl glycolipids and may have roles in the innate and adaptative immune systems to protect against various antigens expressing α-mannosyl glycolipids and to regulate the adaptive immune system responding to the intracellular ligands.