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Science 18 July 1997:
Vol. 277. no. 5324, pp. 339 - 345
DOI: 10.1126/science.277.5324.339
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Research Articles

Crystal Structure of Mouse CD1: An MHC-Like Fold with a Large Hydrophobic Binding Groove

Z.-H. Zeng, * A. R. Castaño, dagger B. W. Segelke, E. A. Stura, P. A. Peterson, I. A. Wilson ddagger

CD1 represents a third lineage of antigen-presenting molecules that are distantly related to major histocompatibility complex (MHC) molecules in the immune system. The crystal structure of mouse CD1d1, corresponding to human CD1d, at 2.8 Å resolution shows that CD1 adopts an MHC fold that is more closely related to that of MHC class I than to that of MHC class II. The binding groove, although significantly narrower, is substantially larger because of increased depth and it has only two major pockets that are almost completely hydrophobic. The extreme hydrophobicity and shape of the binding site are consistent with observations that human CD1b and CD1c can present mycobacterial cell wall antigens, such as mycolic acid and lipoarabinomannans. However, mouse CD1d1 can present very hydrophobic peptides, but must do so in a very different way from MHC class Ia and class II molecules.

Z.-H. Zeng, B. W. Segelke, E. A. Stura, and I. A. Wilson are in the Department of Molecular Biology and the Skaggs Institute for Chemical Biology at the Scripps Research Institute, La Jolla, CA 92037, USA. A. R. Castaño and P. A. Peterson are at the R. W. Johnson Pharmaceutical Research Institute at the Scripps Research Institute, La Jolla, CA 92037, USA.
*   Present address: Department of Protein Engineering, Institute of Biophysics, Chinese Academy of Sciences, Chao Yang District, Beijing 100101, China.

dagger    Present address: Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, Ctra Pozuelo Km2, 28220 Majadahonda (Madrid), Spain.

ddagger    To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu

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   Abstract »    Full Text »
Glycosyl-Phosphatidylinositol Reanchoring Unmasks Distinct Antigen-Presenting Pathways for CD1b and CD1c.
D. H. Geho, J. D. Fayen, R. M. Jackman, D. B. Moody, S. A. Porcelli, and M. L. Tykocinski (2000)
J. Immunol. 165, 1272-1277
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In Vivo Identification of Glycolipid Antigen-Specific T Cells Using Fluorescent Cd1d Tetramers.
K. Benlagha, A. Weiss, A. Beavis, L. Teyton, and A. Bendelac (2000)
J. Exp. Med. 191, 1895-1904
   Abstract »    Full Text »    PDF »
Cutting Edge: The IgG Response to the Circumsporozoite Protein Is MHC Class II-Dependent and CD1d-Independent: Exploring the Role of GPIs in NK T Cell Activation and Antimalarial Responses.
A. Molano, S.-H. Park, Y.-H. Chiu, S. Nosseir, A. Bendelac, and M. Tsuji (2000)
J. Immunol. 164, 5005-5009
   Abstract »    Full Text »    PDF »
Cd1, Tuberculosis, and the Evolution of Major Histocompatibility Complex Molecules.
K. Shinkai and R. M. Locksley (2000)
J. Exp. Med. 191, 907-914
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Self-Recognition of Cd1 by {gamma}/{delta} T Cells: Implications for Innate Immunity.
F. M. Spada, E. P. Grant, P. J. Peters, M. Sugita, A. Melian, D. S. Leslie, H. K. Lee, E. van Donselaar, D. A. Hanson, A. M. Krensky, et al. (2000)
J. Exp. Med. 191, 937-948
   Abstract »    Full Text »    PDF »
NKT Cells in the Rat: Organ-Specific Distribution of NK T Cells Expressing Distinct V{alpha}14 Chains.
A. Matsuura, M. Kinebuchi, H.-Z. Chen, S. Katabami, T. Shimizu, Y. Hashimoto, K. Kikuchi, and N. Sato (2000)
J. Immunol. 164, 3140-3148
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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
   Abstract »    Full Text »    PDF »
Lipoglycans Are Putative Ligands for the Human Pulmonary Surfactant Protein A Attachment to Mycobacteria. CRITICAL ROLE OF THE LIPIDS FOR LECTIN-CARBOHYDRATE RECOGNITION.
S. Sidobre, J. Nigou, G. Puzo, and M. Riviere (2000)
J. Biol. Chem. 275, 2415-2422
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Crystal Structure of a T Cell Receptor Ligand T22: A Truncated MHC-Like Fold.
C. Wingren, M. P. Crowley, I. S. A. M. Degano, Y. Chien, and I. A. Wilson (2000)
Science 287, 310-314
   Abstract »    Full Text »
Mycobacterium tuberculosis H37Rv Parietal and Cellular Lipoarabinomannans. CHARACTERIZATION OF THE ACYL- AND GLYCO-FORMS.
M. Gilleron, L. Bala, T. Brando, A. Vercellone, and G. Puzo (2000)
J. Biol. Chem. 275, 677-684
   Abstract »    Full Text »    PDF »
Conservation of a CD1 Multigene Family in the Guinea Pig.
C. C. Dascher, K. Hiromatsu, J. W. Naylor, P. P. Brauer, K. A. Brown, J. R. Storey, S. M. Behar, E. S. Kawasaki, S. A. Porcelli, M. B. Brenner, et al. (1999)
J. Immunol. 163, 5478-5488
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Structural prediction and analysis of endothelial cell protein C/activated protein C receptor.
B. O. Villoutreix, A. M. Blom, and B. Dahlback (1999)
Protein Eng. Des. Sel. 12, 833-840
   Abstract »    Full Text »    PDF »
Analysis of the early biogenesis of CD1b: involvement of the chaperones calnexin and calreticulin, the proteasome and {beta}2-microglobulin.
R. Huttinger, G. Staffler, O. Majdic, and H. Stockinger (1999)
Int. Immunol. 11, 1615-1623
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The Nonclassical Class I Molecule CD1d Associates with the Novel CD8 Ligand gp180 on Intestinal Epithelial Cells.
N. A. Campbell, H. S. Kim, R. S. Blumberg, and L. Mayer (1999)
J. Biol. Chem. 274, 26259-26265
   Abstract »    Full Text »    PDF »
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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H2-M3-Restricted T Cells in Bacterial Infection: Rapid Primary but Diminished Memory Responses.
K. M. Kerksiek, D. H. Busch, I. M. Pilip, S. E. Allen, and E. G. Pamer (1999)
J. Exp. Med. 190, 195-204
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Structural and Functional Implications of the Intron/Exon Organization of the Human Endothelial Cell Protein C/Activated Protein C Receptor (EPCR) Gene: Comparison With the Structure of CD1/Major Histocompatibility Complex alpha 1 and alpha 2 Domains.
R. E. Simmonds and D. A. Lane (1999)
Blood 94, 632-641
   Abstract »    Full Text »    PDF »
A novel recognition motif of human NKT antigen receptor for a glycolipid ligand.
T. Kawano, Y. Tanaka, E. Shimizu, Y. Kaneko, N. Kamata, H. Sato, H. Osada, S. Sekiya, T. Nakayama, and M. Taniguchi (1999)
Int. Immunol. 11, 881-887
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Tissue-Specific Segregation of CD1d-Dependent and CD1d-Independent NK T Cells.
G. Eberl, R. Lees, S. T. Smiley, M. Taniguchi, M. J. Grusby, and H. R. MacDonald (1999)
J. Immunol. 162, 6410-6419
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Molecular Cloning and Characterization of a Novel CD1 Gene from the Pig.
T. Chun, K. Wang, F. A. Zuckermann, and H. R. Gaskins (1999)
J. Immunol. 162, 6562-6571
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Expression of CD1d2 on Thymocytes Is Not Sufficient for the Development of NK T Cells in CD1d1-Deficient Mice.
Y.-H. Chen, B. Wang, T. Chun, L. Zhao, S. Cardell, S. M. Behar, M. B. Brenner, and C.-R. Wang (1999)
J. Immunol. 162, 4560-4566
   Abstract »    Full Text »    PDF »


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