期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 199, 期 5, 页码 649-659出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20031097
关键词
vaccination; intracellular bacteria; protection; cytotoxic CD8(+) T cells; lipids
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-palinitoyl or 2-stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-alpha-alpha'-D-trehalose (Ac(2)SGL). Its immunogenicity is dependent on the presence of the sulfate group and of the two fatty acids. Ac(2)SGL is mainly presented by CD1b molecules after internalization in a cellular compartment with low pH. Ac(2)SGL-specific T cells release interferon gamma, efficiently recognize M. tuberculosis-infected cells, and kill intracellular bacteria. The presence of Ac(2)SGL-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 Ac(2)SGL as a promising candidate to be tested in novel vaccines against tuberculosis.
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