1. Lysosomal glycosphingolipid recognition by NKT cells
- Author
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Zhou, Dapeng, Mattner, Jochen, Cantu, III, Carlos, Schrantz, Nicolas, Yin, Ning, Gao, Ying, Sagiv, Yuval, Hudspeth, Kelly, Wu, Yun-Ping, Yamashita, Tadashi, Teneberg, Susann, Wang, Dacheng, Proia, Richard L., Levery, Steven B., Savage, Paul B., Teyton, Luc, and Bendelac, Albert
- Subjects
T cells -- Research ,Killer cells -- Research ,Lysosomes -- Research ,Science and technology ,Research - Abstract
NKT cells represent a distinct lineage of T cells that coexpress a conserved αβ T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking β-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity., As with protein-derived antigens, lipids, glycolipids, and lipopeptides (either of microbial or self origin) can be recognized by TCRαβ-expressing T lymphocytes (1). Of these, NKT cells represent an unusual population [...]
- Published
- 2004