Editors' ChoiceImmunology

Giving a Self-Antigen Its Natural Identity

Science's STKE  07 Dec 2004:
Vol. 2004, Issue 262, pp. tw439
DOI: 10.1126/stke.2622004tw439

Natural killer (NK) T cells recognize lipids, rather than protein-derived antigens, that are presented by major histocompatibility class 1-like CD1 molecules. Although certain artificial lipids and a handful derived from bacteria have been shown to stimulate NKT cells, the identity of naturally occurring endogenous lipid ligands has been elusive. Zhou et al. (see the Perspective by Godfrey et al.) now reveal that a single mammalian lysosomal glycosphingolipid, isoglobotrihexosylceramide, or iGb3, can stimulate large numbers of human and mouse NKT cells, and they found that mice lacking a subunit of an enzyme responsible for generating iGb3 have a profound deficiency in NKT cell development in the thymus. This lipid antigen may thus play a role in directing NKT cell development and function and may contribute to a variety of disease states, from infection to cancer.

D. Zhou, J. Mattner, C. Cantu III, N. Schrantz, N. Yin, Y. Gao, Y. Sagiv, K. Hudspeth, Y.-P. Wu, T. Yamashita, S. Teneberg, D. Wang, R. L. Proia, S. B. Levery, P. B. Savage, L. Teyton, A. Bendelac, Lysosomal glycosphingolipid recognition by NKT cells. Science 306, 1786-1789 (2004). [Abstract] [Full Text]

D. I. Godfrey, D. G. Pellicci, M. J. Smyth, The elusive NKT cell antigen--Is the search over? Science 306, 1687-1689 (2004). [Summary] [Full Text]