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Science 6 March 1998:
Vol. 279. no. 5356, pp. 1541 - 1544
DOI: 10.1126/science.279.5356.1541
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Reports

Natural Ligand of Mouse CD1d1: Cellular Glycosylphosphatidylinositol

Sebastian Joyce, * Amina S. Woods, Jonathan W. Yewdell, Jack R. Bennink, A. Dharshan De Silva, Alina Boesteanu, Steven P. Balk, Robert J. Cotter, Randy R. Brutkiewicz

Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen-like molecules, controls the differentiation and function of a T lymphocyte subset, NK1+ natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical nature. Mass spectrometry and metabolic radiolabeling were used to identify cellular glycosylphosphatidylinositol as a major natural ligand of CD1d1. CD1d1 bound glycosylphosphatidylinositol through its phosphatidylinositol aspect with high affinity. Glycosylphosphatidylinositol or another glycolipid could be a candidate natural ligand for CD1d1-restricted T cells.

S. Joyce, A. D. De Silva, A. Boesteanu, Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA.
A. S. Woods and R. J. Cotter, Departments of Oncology and Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
J. W. Yewdell, J. R. Bennink, R. R. Brutkiewicz, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0440, USA.
S. P. Balk, Hematology-Oncology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
*   To whom correspondence should be addressed. E-mail: sjoyce{at}bcmic.hmc.psu.edu

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J. Exp. Med. 191, 937-948
   Abstract »    Full Text »    PDF »
Liver CD4-CD8- NK1.1+ TCR{alpha}{beta} Intermediate Cells Increase During Experimental Malaria Infection and Are Able to Exhibit Inhibitory Activity Against the Parasite Liver Stage In Vitro.
S. Pied, J. Roland, A. Louise, D. Voegtle, V. Soulard, D. Mazier, and P.-A. Cazenave (2000)
J. Immunol. 164, 1463-1469
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Comparative Contribution of CD1 on the Development of CD4+ and CD8+ T Cell Compartments.
B. Wang, T. Chun, and C.-R. Wang (2000)
J. Immunol. 164, 739-745
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Heterogeneity of NK1.1+ T Cells in the Bone Marrow: Divergence from the Thymus.
D. Zeng, G. Gazit, S. Dejbakhsh-Jones, S. P. Balk, S. Snapper, M. Taniguchi, and S. Strober (1999)
J. Immunol. 163, 5338-5345
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Immune Privilege: Keeping an Eye on Natural Killer T Cells.
S. Hong and L. Van Kaer (1999)
J. Exp. Med. 190, 1197-1200
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Impaired NK1.1 T Cell Development in Mice Transgenic for a T Cell Receptor {beta} Chain Lacking the Large, Solvent-exposed C{beta} FG Loop.
S. Degermann, G. Sollami, and K. Karjalainen (1999)
J. Exp. Med. 190, 1357-1362
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Binding and Antigen Presentation of Ceramide-containing Glycolipids by Soluble Mouse and Human CD1d Molecules.
O. V. Naidenko, J. K. Maher, W. A. Ernst, T. Sakai, R. L. Modlin, and M. Kronenberg (1999)
J. Exp. Med. 190, 1069-1080
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Thermolabile H-2Kb Molecules Expressed by Transporter Associated with Antigen Processing-Deficient RMA-S Cells Are Occupied by Low-Affinity Peptides.
A. D. De Silva, A. Boesteanu, R. Song, N. Nagy, E. Harhaj, C. V. Harding, and S. Joyce (1999)
J. Immunol. 163, 4413-4420
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Inhibition of T Helper Cell Type 2 Cell Differentiation and Immunoglobulin E Response by Ligand-activated V{alpha}14 Natural Killer T Cells.
J. Cui, N. Watanabe, T. Kawano, M. Yamashita, T. Kamata, C. Shimizu, M. Kimura, E. Shimizu, J. Koike, H. Koseki, et al. (1999)
J. Exp. Med. 190, 783-792
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CD1 Expression in Human Atherosclerosis : A Potential Mechanism for T Cell Activation by Foam Cells.
A. Melian, Y.-J. Geng, G. K. Sukhova, P. Libby, and S. A. Porcelli (1999)
Am. J. Pathol. 155, 775-786
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Cutting Edge: Activation of NK T Cells by CD1d and {alpha}-Galactosylceramide Directs Conventional T Cells to the Acquisition of a Th2 Phenotype.
N. Singh, S. Hong, D. C. Sc