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 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.
Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale du CNRS, Toulouse 31077, Cedex 4, France.
Martine
M
Gilleron
Steffen
S
Stenger
Zaima
Z
Mazorra
Frederick
F
Wittke
Sabrina
S
Mariotti
Gabriele
G
Böhmer
Jacques
J
Prandi
Lucia
L
Mori
Germain
G
Puzo
Gennaro
G
De Libero
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000737:chemistry; D018949:Antigens, CD1 / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D006017:Glycolipids; C011117:sulfoglycolipids