KRN7000 mechanism
KRN7000, a glycolipid derived from the marine sponge has a novel α-galactosylceramide (α-GalCer) structure and exhibits potent anti-tumor activity by stimulating a strong immune response. Natural Killer T Cells (NKT cells) serve as an important role regulating the immune response and in the presence of KRN7000 stimulate NKT cells to releasing a rapid production of Th1 and Th2 cytokines including IL-4, IL-10, IL-13 and IFN-gama (1,2) strongly enhancing the immune system against tumors, autoimmune diseases, viral, bacterial and parasites. It has been experimentally determined that KRN7000 is presented by CD1d and works as a ligand to the invariant Vα 14 T cell receptor of mouse NK1.1+ Vα14Jα281β T cell receptor+ (NKT) cells (3,4) and the invariant Vα24JαQVβ11 T cell receptor of human NKT cells (5). The KRN7000 biochemical mechanism triggering the immune response has not been fully characterized and investigators continue to to understand the underlying mechanism.

Alpha-GalCer complexed with CD1d.
Graphic file from Universite De Reims
1) Godfrey, D. I., Hammond, K. J., Poulton, L. D., Smyth, M.J. & Baxter, A. G. (2000) Immunol. Today 21, 573-583.
2) Smyth, M. J. & Godfrey, D. I. (2000) Nat. Immunol. 1, 459-460.
3) Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kancko, Y., Sato, H., Kondo, E., Harada, M., Koseki, H., Nakayama, T., et al (1998) Proc. Natl. Acad. Sci. USA 95, 5690-5693.
4) Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kaneko, Y., Motoki, K., Ueno, H., Nakagawa, R., Sato, H., Kondo, E., et al. (1997) Science 278, 1626-1629.

