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Science 23 January 2004:
Vol. 303. no. 5657, pp. 527 - 531
DOI: 10.1126/science.1089353
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Reports

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

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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Science. ISSN 0036-8075 (print), 1095-9203 (online)