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Published Online November 11, 2004
Science DOI: 10.1126/science.1103440

Reports

Submitted on July 30, 2004
Accepted on October 22, 2004

Lysosomal Glycosphingolipid Recognition by NKT cells

Dapeng Zhou 1*, Jochen Mattner 1, Carlos Cantu III 2, Nicolas Schrantz 2, Ning Yin 3, Ying Gao 3, Yuval Sagiv 1, Kelly Hudspeth 1, Yunping Wu 4, Tadashi Yamashita 4, Susann Teneberg 5, Dacheng Wang 6, Richard Proia 4, Steven B. Levery 7, Paul B. Savage 3, Luc Teyton 2, Albert Bendelac 1*

1 University of Chicago, Department of Pathology, Chicago, IL 60637, USA.
2 The Scripps Research Institute, Department of Immunology, La Jolla, CA 92037, USA.
3 Brigham Young University, Department of Chemistry and Biochemistry, Provo, UT 84602-5700, USA.
4 Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
5 Institute of Medical Biochemistry, Göteborg University, SE 405 30 Göteborg, Sweden.
6 Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P. R. China.
7 Department of Chemistry, University of New Hampshire, Durham, NH 03824-3598, USA.

* To whom correspondence should be addressed.
Dapeng Zhou , E-mail: dzhou{at}midway.uchicago.edu
Albert Bendelac , E-mail: abendela{at}bsd.uchicago.edu

NKT cells represent a distinct lineage of T cells that coexpress a conserved {alpha}{beta}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 {beta}-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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J. Immunol. 177, 3484-3492
   Abstract »    Full Text »    PDF »
Improving Antitumor Immune Responses by Circumventing Immunoregulatory Cells and Mechanisms..
G. Lizee, L. G. Radvanyi, W. W. Overwijk, and P. Hwu (2006)
Clin. Cancer Res. 12, 4794-4803
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Glycolipid {alpha}-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice.
S.-i. Fujii, K. Shimizu, H. Hemmi, M. Fukui, A. J. Bonito, G. Chen, R. W. Franck, M. Tsuji, and R. M. Steinman (2006)
PNAS 103, 11252-11257
   Abstract »    Full Text »    PDF »
CD1d Ligands: The Good, the Bad, and the Ugly.
R. R. Brutkiewicz (2006)
J. Immunol. 177, 769-775
   Abstract »    Full Text »    PDF »
Effective gene therapy in an authentic model of Tay-Sachs-related diseases.
M. B. Cachon-Gonzalez, S. Z. Wang, A. Lynch, R. Ziegler, S. H. Cheng, and T. M. Cox (2006)
PNAS 103, 10373-10378
   Abstract »    Full Text »    PDF »
CD1d-Restricted T Cells License B Cells to Generate Long-Lasting Cytotoxic Antitumor Immunity In vivo..
Y. Chung, B.-S. Kim, Y.-J. Kim, H.-J. Ko, S.-Y. Ko, D.-H. Kim, and C.-Y. Kang (2006)
Cancer Res. 66, 6843-6850
   Abstract »    Full Text »    PDF »
Cutting Edge: Impaired Glycosphingolipid Trafficking and NKT Cell Development in Mice Lacking Niemann-Pick Type C1 Protein.
Y. Sagiv, K. Hudspeth, J. Mattner, N. Schrantz, R. K. Stern, D. Zhou, P. B. Savage, L. Teyton, and A. Bendelac (2006)
J. Immunol. 177, 26-30
   Abstract »    Full Text »    PDF »
T-cell recognition of glycolipids presented by CD1 proteins.
D. C. Young and D. B. Moody (2006)
Glycobiology 16, 103R-112R
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The Complementarity Determining Region 2 of BV8S2 (Vbeta8.2) Contributes to Antigen Recognition by Rat Invariant NKT Cell TCR..
E. Pyz, O. Naidenko, S. Miyake, T. Yamamura, I. Berberich, S. Cardell, M. Kronenberg, and T. Herrmann (2006)
J. Immunol. 176, 7447-7455
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A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells.
A. S. Franki, K. Van Beneden, P. Dewint, K. J. L. Hammond, S. Lambrecht, G. Leclercq, M. Kronenberg, D. Deforce, and D. Elewaut (2006)
PNAS 103, 9160-9165
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Mechanisms imposing the V{beta} bias of V{alpha}14 natural killer T cells and consequences for microbial glycolipid recognition.
D. G. Wei, S. A. Curran, P. B. Savage, L. Teyton, and A. Bendelac (2006)
J. Exp. Med. 203, 1197-1207
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Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells.
Y. Campos-Martin, M. Colmenares, B. Gozalbo-Lopez, M. Lopez-Nunez, P. B. Savage, and E. Martinez-Naves (2006)
J. Immunol. 176, 6172-6179
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Oral nickel tolerance: fas ligand-expressing invariant NK T cells promote tolerance induction by eliciting apoptotic death of antigen-carrying, effete B cells..
M. Nowak, F. Kopp, K. Roelofs-Haarhuis, X. Wu, and E. Gleichmann (2006)
J. Immunol. 176, 4581-4589
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DOCK2 Is Required in T Cell Precursors for Development of V{alpha}14 NK T Cells..
Y. Kunisaki, Y. Tanaka, T. Sanui, A. Inayoshi, M. Noda, T. Nakayama, M. Harada, M. Taniguchi, T. Sasazuki, and Y. Fukui (2006)
J. Immunol. 176, 4640-4645
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