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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}rics.bwh.harvard.edu

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