Lysosomal Glycosphingolipid Recognition by NKT Cells

American Association for the Advancement of Science (AAAS) - Tập 306 Số 5702 - Trang 1786-1789 - 2004
Dapeng Zhou1,2,3,4,5, Jochen Mattner1,2,3,4,5, Carlos Cantu1,2,3,4, Nicolas Schrantz1,2,3,4, Ning Yin1,2,3,4,5, Ying Gao1,2,3,4,5, Yuval Sagiv1,2,3,4,5, Kelly Hudspeth1,2,3,4,5, Yun-Ping Wu1,2,3,4, Tadashi Yamashita1,2,3,4, Susann Teneberg1,2,3,4,5, Dacheng Wang1,2,3,4,5, Richard L. Proia1,2,3,4, Steven B. Levery1,2,3,4,5, Paul B. Savage1,2,3,4,5, Luc Teyton1,2,3,4, Albert Bendelac1,2,3,4,5
1Brigham Young University, Department of Chemistry and Biochemistry, Provo, UT 84602–5700, USA.
2Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
3Institute of Medical Biochemistry, Göteborg University, SE 405 30 Göteborg, Sweden.
4The Scripps Research Institute, Department of Immunology, La Jolla, CA 92037, USA
5University of Chicago, Department of Pathology, Chicago, IL 60637, USA.

Tóm tắt

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.

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Tài liệu tham khảo

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This work was supported by CRI fellowships (D.Z. and Y.S.) and NIH grants (P01 AI053725 to A.B. L.T. and P.B.S. and R01 AI38339 and AI50847 to A.B.). S.T. is supported by Swedish Medical Research Council (no. 12628) and the Swedish Cancer Foundation. S.B.L. is supported by the New Hampshire Biological Research Infrastructure Network-Center for structural biology (NIH P20RR16459). We thank C. Borowski A. Chong U. Galili K. Hayakawa T. Henion F.-F. Hsu B. Jabri P. Matzinger and B. Meresse for advice and help with reagents and C. Bowers for mouse care.

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American Association for the Advancement of Science (AAAS)

Tập 306 Số 5702

1786-1789

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