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Science 10 October 1997:
Vol. 278. no. 5336, pp. 283 - 286
DOI: 10.1126/science.278.5336.283
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Reports

Structural Requirements for Glycolipid Antigen Recognition by CD1b-Restricted T Cells

D. Branch Moody, Bruce B. Reinhold, Mark R. Guy, Evan M. Beckman, * Daphney E. Frederique, Stephen T. Furlong, dagger Song Ye, Vernon N. Reinhold, Peter A. Sieling, Robert L. Modlin, Gurdyal S. Besra, Steven A. Porcelli ddagger

The human CD1b protein presents lipid antigens to T cells, but the molecular mechanism is unknown. Identification of mycobacterial glucose monomycolate (GMM) as a CD1b-presented glycolipid allowed determination of the structural requirements for its recognition by T cells. Presentation of GMM to CD1b-restricted T cells was not affected by substantial variations in its lipid tails, but was extremely sensitive to chemical alterations in its carbohydrate or other polar substituents. These findings support the view that the recently demonstrated hydrophobic CD1 groove binds the acyl chains of lipid antigens relatively nonspecifically, thereby positioning the hydrophilic components for highly specific interactions with T cell antigen receptors.

D. B. Moody, E. M. Beckman, D. E. Frederique, S. T. Furlong, S.A. Porcelli, Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
B. B. Reinhold, S. Ye, V. N. Reinhold, Mass Spectrometry Unit, Boston University School of Medicine, Boston, MA 02118-2394, USA.
M. R. Guy and G. S. Besra, Department of Microbiology, Colorado State University, Fort Collins, CO 80523-1677, USA.
P.A. Sieling and R. L. Modlin, Division of Dermatology and Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA 90033, USA.
*   Present address: Biogen, 14 Cambridge Center, Cambridge, MA 02142, USA.

dagger    Present address:. Zeneca Pharmaceuticals, Wilmington, DE 19803, USA.

ddagger    To whom correspondence should be addressed. E-mail: sporcelli{at}rics.bwh.harvard.edu

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Colorectal Cancer as a Model for Immunotherapy.
K. A. Foon, J. Yannelli, and M. Bhattacharya-Chatterjee (1999)
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CD1 Expression by Dendritic Cells in Human Leprosy Lesions: Correlation with Effective Host Immunity.
P. A. Sieling, D. Jullien, M. Dahlem, T. F. Tedder, T. H. Rea, R. L. Modlin, and S. A. Porcelli (1999)
J. Immunol. 162, 1851-1858
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CD1d-Restricted Immunoglobulin G Formation to GPI-Anchored Antigens Mediated by NKT Cells.
L. Schofield, M. J. McConville, D. Hansen, A. S. Campbell, B. Fraser-Reid, M. J. Grusby, and S. D. Tachado (1999)
Science 283, 225-229
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Distinct Subsets of CD1d-restricted T Cells Recognize Self-antigens Loaded in Different Cellular Compartments.
Y.-H. Chiu, J. Jayawardena, A. Weiss, D. Lee, S.-H. Park, A. Dautry-Varsat, and A. Bendelac (1999)
J. Exp. Med. 189, 103-110
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Molecular Recognition of Lipid Antigens by T Cell Receptors.
E. P. Grant, M. Degano, J.-P. Rosat, S. Stenger, R. L. Modlin, I. A. Wilson, S. A. Porcelli, and M. B. Brenner (1999)
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Diverse TCRs Recognize Murine CD1.
S. M. Behar, T. A. Podrebarac, C. J. Roy, C. R. Wang, and M. B. Brenner (1999)
J. Immunol. 162, 161-167
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Cutting Edge: Structural Requirements for Galactosylceramide Recognition by CD1-Restricted NK T Cells.
L. Brossay, O. Naidenko, N. Burdin, J. Matsuda, T. Sakai, and M. Kronenberg (1998)
J. Immunol. 161, 5124-5128
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CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells.
F. M. Spada, Y. Koezuka, and S. A. Porcelli (1998)
J. Exp. Med. 188, 1529-1534
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Selective Ability of Mouse CD1 to Present Glycolipids: {alpha}-Galactosylceramide Specifically Stimulates V{alpha}14+ NK T Lymphocytes.
N. Burdin, L. Brossay, Y. Koezuka, S. T. Smiley, M. J. Grusby, M. Gui, M. Taniguchi, K. Hayakawa, and M. Kronenberg (1998)
J. Immunol. 161, 3271-3281
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CD1c molecules broadly survey the endocytic system.
M. Sugita, N. van der Wel, R. A. Rogers, P. J. Peters, and M. B. Brenner (2000)
PNAS 97, 8445-8450
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Presentation of the Same Glycolipid by Different CD1 Molecules.
A. Shamshiev, H.-J. Gober, A. Donda, Z. Mazorra, L. Mori, and G. De Libero (2002)
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