Lysosomal glycosphingolipid recognition by NKT cells

Dapeng Zhou, Jochen Mattner, Carlos Cantu, Nicolas Schrantz, Ning Yin, Ying Gao, Yuval Sagiv, Kelly Hudspeth, Yun Ping Wu, Tadashi Yamashita, Susann Teneberg, Dacheng Wang, Richard L. Proia, Steven B. Levery, Paul B. Savage, Luc Teyton, Albert Bendelac

Research output: Contribution to journalArticlepeer-review

Abstract

NKT cells represent a distinct lineage of T cells that coexpress a conserved αβT 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.

Original languageEnglish
Pages (from-to)1786-1789
Number of pages4
JournalScience
Volume306
Issue number5702
DOIs
Publication statusPublished - Dec 3 2004

ASJC Scopus subject areas

  • General

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