Diacylated sulfoglycolipids are novel mycobacterial antigens stimulating CD1-restricted T cells during infection with Mycobacterium tuberculosis

Mycobacterial lipids comprise a heterogeneous group of molecules capable of inducing T cell responses in humans. To identify novel antigenic lipids and increase our understanding of lipid-mediated immune responses, we established a panel of T cell clones with different lipid specificities. Using thi...

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Published inThe Journal of experimental medicine Vol. 199; no. 5; pp. 649 - 659
Main Authors Gilleron, Martine, Stenger, Steffen, Mazorra, Zaima, Wittke, Frederick, Mariotti, Sabrina, Böhmer, Gabriele, Prandi, Jacques, Mori, Lucia, Puzo, Germain, De Libero, Gennaro
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 01.03.2004
The Rockefeller University Press
Subjects
Adaptive immunology
Antigen Presentation
Antigens, Bacterial
Antigens, Bacterial - chemistry
Antigens, CD1
Antigens, CD1 - metabolism
Biochemistry
Biochemistry, Molecular Biology
CD8-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes - immunology
Cell Line
Glycolipids
Glycolipids - chemistry
Glycolipids - immunology
Humans
Immunology
Life Sciences
Lymphocyte Activation
Molecular Structure
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Mycobacterium tuberculosis - pathogenicity
Structural Biology
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Summary:Mycobacterial lipids comprise a heterogeneous group of molecules capable of inducing T cell responses in humans. To identify novel antigenic lipids and increase our understanding of lipid-mediated immune responses, we established a panel of T cell clones with different lipid specificities. Using this approach we characterized a novel lipid antigen belonging to the group of diacylated sulfoglycolipids purified from Mycobacterium tuberculosis. The structure of this sulfoglycolipid was identified as 2-palmitoyl or 2-stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-alpha-alpha'-D-trehalose (Ac2SGL). Its immunogenicity is dependent on the presence of the sulfate group and of the two fatty acids. Ac2SGL is mainly presented by CD1b molecules after internalization in a cellular compartment with low pH. Ac2SGL-specific T cells release interferon gamma, efficiently recognize M. tuberculosis-infected cells, and kill intracellular bacteria. The presence of Ac2SGL-responsive T cells in vivo is strictly dependent on previous contact with M. tuberculosis, but independent from the development of clinically overt disease. These properties identify Ac2SGL as a promising candidate to be tested in novel vaccines against tuberculosis.
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PMCID: PMC2213295
Z. Mazorra's present address is Center of Molecular Immunology, P.O. Box 16040, Havana, 11600 Cuba.
Abbreviations used in this paper: 1H NMR, proton nuclear magnetic resonance; Ac2SGL, 2-palmitoyl or 2-stearoyl-3-hydroxyphthioceranoyl-2′-sulfate-α-α′-d-trehalose; BCG, bacillus Calmette Guérin; MALDI-Tof-MS, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry; m/z, mass/charge; NMR, nuclear magnetic resonance; PIM, phosphatidyl-myo-inositol mannosides; PPD, purified protein derivative of M. tuberculosis; SGL, sulfoglycolipids.
The online version of this article contains supplemental material.
M. Gilleron, S. Stenger, and Z. Mazorra contributed equally to this work.
Address correspondence to Gennaro De Libero, Experimental Immunology, Department of Research, University Hospital, Hebelstrasse 20, Basel CH-4031, Switzerland. Phone: 41-61-265-23-27; Fax: 41-61-265-23-50; email: Gennaro.DeLibero@unibas.ch; or Germain Puzo, Institut de Pharmacologie et de Biologie Structurale du CNRS, Département Mécanismes Moléculaires des Infections Mycobactériennes, 205 route de Narbonne, Toulouse 31077, Cedex 4, France. Phone: 33-56-1175504; Fax: 33-561175505; email: Germain.Puzo@ipbs.fr
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20031097