Activation of human Vα24NKT cells by α-glycosylceramide in a CD1d-restricted and Vα24TCR-mediated manner

Abstract

Vα14NK(natural killer) T cells play an important role in controlling tumors or in preventing autoimmunity in the murine system. Vα24NKT cells, the human counterpart of Vα14NKT cells, may contribute to controlling the progression of autoimmune diseases in humans. These findings show the possibility that ligand(s) for these NKT cells can control the above-mentioned pathological conditions. Specific glycolipids such as α-galactosylceramide (α-GalCer) and α-glucosylceramide (α-GlcCer) have been identified as ligand(s) recognized by murine Vα14NKT cells in a CD1d-restricted manner, but it remains unclear whether these glycolipids are ligand(s) for Vα24NKT cells in humans. To determine whether α-glycosylceramide is presented by CD1d molecules in humans, we initially established a Vα24NKT cell line specific for α-glycosylceramide using dendritic cell (DC) like cells from normal peripheral blood mononuclear cells (PBMC) in an autologous mixed leukocyte reaction (auto-MLR) system, and characterized the Vα24NKT cell line. The Vα24NKT cells were CD3+CD4−CD8−Vα24+Vβ11+NKRP1A+ and specifically proliferated in response to α-glycosylceramide in CD1d-restricted and Vα24TCR-mediated manner. The phenotypic and functional similarities between murine Vα14NKT cells and human Vα24NKT cells suggest that Vα24NKT cells may play an important role in controlling tumors or in preventing autoimmunity as observed with Vα14NKT cells.