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Science 303 (5657): 527-531

Copyright © 2004 by the American Association for the Advancement of Science

T Cell Activation by Lipopeptide Antigens

D. Branch Moody,1* David C. Young,1,2 Tan-Yun Cheng,1 Jean-Pierre Rosat,1 Carme Roura-mir,1 Peter B. O'Connor,2 Dirk M. Zajonc,5 Andrew Walz,3 Marvin J. Miller,3 Steven B. Levery,4 Ian A. Wilson,5,6 Catherine E. Costello,2 Michael B. Brenner1

Abstract: Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the {alpha}ß T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.

1 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Smith Building Room 514, 1 Jimmy Fund Way, Boston, MA 02115, USA.
2 Mass Spectrometry Resource, Boston University School of Medicine, 715 Albany Street, R806, Boston, MA 02115, USA.
3 Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556–5670, USA.
4 Department of Chemistry, University of New Hampshire, Durham, NH 02834, USA.
5 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
6 Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: bmoody{at}

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J. Bacteriol. 193, 441-448
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CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice.
K. Felio, H. Nguyen, C. C. Dascher, H.-J. Choi, S. Li, M. I. Zimmer, A. Colmone, D. B. Moody, M. B. Brenner, and C.-R. Wang (2009)
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Synthesis of Dideoxymycobactin Antigens Presented by CD1a Reveals T Cell Fine Specificity for Natural Lipopeptide Structures.
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CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids.
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Fatty Acyl Structures of Mycobacterium tuberculosis Sulfoglycolipid Govern T Cell Response.
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Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans.
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J. Immunol. 180, 3436-3446
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Siderophore-Based Iron Acquisition and Pathogen Control.
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Role of lipid trimming and CD1 groove size in cellular antigen presentation.
T.-Y. Cheng, M. Relloso, I. Van Rhijn, D. C. Young, G. S. Besra, V. Briken, D. M. Zajonc, I. A. Wilson, S. Porcelli, and D. B. Moody (2006)
EMBO J. 25, 2989-2999
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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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D. Wu, D. M. Zajonc, M. Fujio, B. A. Sullivan, Y. Kinjo, M. Kronenberg, I. A. Wilson, and C.-H. Wong (2006)
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A Major Cell Wall Lipopeptide of Mycobacterium avium subspecies paratuberculosis.
T. M. Eckstein, S. Chandrasekaran, S. Mahapatra, M. R. McNeil, D. Chatterjee, C. D. Rithner, P. W. Ryan, J. T. Belisle, and J. M. Inamine (2006)
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R. Krithika, U. Marathe, P. Saxena, Mohd. Z. Ansari, D. Mohanty, and R. S. Gokhale (2006)
PNAS 103, 2069-2074
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T. Kolter, F. Winau, U. E. Schaible, M. Leippe, and K. Sandhoff (2005)
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Assistance of Microbial Glycolipid Antigen Processing by CD1e.
H. de la Salle, S. Mariotti, C. Angenieux, M. Gilleron, L.-F. Garcia-Alles, D. Malm, T. Berg, S. Paoletti, B. Maitre, L. Mourey, et al. (2005)
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M. S. Vincent, X. Xiong, E. P. Grant, W. Peng, and M. B. Brenner (2005)
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J. Exp. Med. 202, 529-539
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Mycobacterium tuberculosis Regulates CD1 Antigen Presentation Pathways through TLR-2.
C. Roura-Mir, L. Wang, T.-Y. Cheng, I. Matsunaga, C. C. Dascher, S. L. Peng, M. J. Fenton, C. Kirschning, and D. B. Moody (2005)
J. Immunol. 175, 1758-1766
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Human CD1-restricted T cell recognition of lipids from pollens.
E. Agea, A. Russano, O. Bistoni, R. Mannucci, I. Nicoletti, L. Corazzi, A. D. Postle, G. De Libero, S. A. Porcelli, and F. Spinozzi (2005)
J. Exp. Med. 202, 295-308
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PNAS 102, 8668-8673
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CD1a and CD1c Activate Intrathyroidal T Cells during Graves' Disease and Hashimoto's Thyroiditis.
C. Roura-Mir, M. Catalfamo, T.-Y. Cheng, E. Marqusee, G. S. Besra, D. Jaraquemada, and D. B. Moody (2005)
J. Immunol. 174, 3773-3780
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The Human CD1-Restricted T Cell Repertoire Is Limited to Cross-Reactive Antigens: Implications for Host Responses against Immunologically Related Pathogens.
P. A. Sieling, J. B. Torrelles, S. Stenger, W. Chung, A. E. Burdick, T. H. Rea, P. J. Brennan, J. T. Belisle, S. A. Porcelli, and R. L. Modlin (2005)
J. Immunol. 174, 2637-2644
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Mycobacterium tuberculosis pks12 Produces a Novel Polyketide Presented by CD1c to T Cells.
I. Matsunaga, A. Bhatt, D. C. Young, T.-Y. Cheng, S. J. Eyles, G. S. Besra, V. Briken, S. A. Porcelli, C. E. Costello, W. R. Jacobs Jr., et al. (2004)
J. Exp. Med. 200, 1559-1569
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CD1d-restricted T cell activation by nonlipidic small molecules.
I. Van Rhijn, D. C. Young, J. S. Im, S. B. Levery, P. A. Illarionov, G. S. Besra, S. A. Porcelli, J. Gumperz, T.-Y. Cheng, and D. B. Moody (2004)
PNAS 101, 13578-13583
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IMMUNOLOGY: The Robin Hood of Antigen Presentation.
G. De Libero (2004)
Science 303, 485-487
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