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

Abstract

A NKT cell repertoire is characterized by the expression of the Valpha19-Jalpha26 invariant TCR alpha chain (Valpha19 NKT cell). This repertoire, as well as a well-established Valpha14-Jalpha281 invariant TCR alpha(+) NKT cell subset (Valpha14 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 Valpha19 NKT cells. Valpha19 as well as Valpha14 NKT cells exhibited reactivity to alpha-galactosyl ceramide (alpha-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 Valpha19 NKT cells was determined by measuring their immune responses in culture with glycolipids. Comprehensive examinations revealed substantial antigenic activity for Valpha19 NKT cells by alpha-mannosyl ceramide.

Fifteen Years since the Development of KRN7000 – Structure-Activity Relationship Studies on Novel Glycosphingolipids Which Stimulate Natural Killer T Cells

“…There are two exceptions: (i) α-L-Fucosyl ceramides could also stimulate human NKT cells and was as potent as 1, although it belongs to the L-sugar (77). (ii) Vα19Jα26 NKT cells, one of the subset of NKT cells, were specifi cally activated by α-D-mannosyl ceramide as reported by Shimamura and his co-workers (78).…”

Glycosphingolipid Ligands for Invariant Natural Killer T cells as Immunostimulants

“…On the other hand, type-II cells express a diverse TCR and recognize ligands presented on CD1d except for KRN7000 (2). For example, Va19Ja26 NKT cells are activated specifically by a-D-mannosyl ceramide but not by 2 [90]. Type-II NKT cells have functions distinct from type-I, and in this chapter, only the ligands for type-I NKT cells are discussed.…”

Immunomodulatory effect of mushrooms on cytotoxic activity and cytokine production of intestinal lamina propria leukocytes does not necessarily depend on β-glucan contents

“…It may instead be due to the structure of β-glucan, or another component of the extracts may have promoted cytotoxic activity. The ceramide component of some mushrooms has been reported to activate NKT cells (Im et al, 2009;Okamoto et al, 2005;Sharif et al, 2001). However, the mushroom extracts used in this study may contain very little amount of ceramide due to hydrophobic property of the molecule.…”