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.
Gilleron
Martine
M
Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale du CNRS, Toulouse 31077, Cedex 4, France.
Stenger
Steffen
S
Mazorra
Zaima
Z
Wittke
Frederick
F
Mariotti
Sabrina
S
Böhmer
Gabriele
G
Prandi
Jacques
J
Mori
Lucia
L
Puzo
Germain
G
De Libero
Gennaro
G
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