T Cell Activation by Lipopeptide Antigens

Author:

Moody D. Branch12345,Young David C.12345,Cheng Tan-Yun12345,Rosat Jean-Pierre12345,Roura-mir Carme12345,O'Connor Peter B.12345,Zajonc Dirk M.12345,Walz Andrew12345,Miller Marvin J.12345,Levery Steven B.12345,Wilson Ian A.12345,Costello Catherine E.12345,Brenner Michael B.12345

Affiliation:

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.

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 αβ 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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