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CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection

Lookup NU author(s): Dr Sudagar Gurcha, Professor Del Besra

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Abstract

The discovery of the CD1 antigen presentation pathway has expanded the spectrum of T-cell antigens to include lipids, but the range of natural lipid antigens and functions of CD1-restricted T cells in vivo remain poorly understood. Here we show that the T-cell antigen receptor and the CD1c protein mediate recognition of an evolutionarily conserved family of isoprenoid glycolipids whose members include essential components of protein glycosylation and cell-wall synthesis pathways. A CD1c-restricted, mycobacteria-specific T-cell line recognized two previously unknown mycobacterial hexosyl-1-phosphoisoprenoids and structurally related mannosyl- β1-phosphodolichols. Responses to mannosyl-β1-phosphodolichols were common among CD1c-restricted T-cell lines and peripheral blood T lymphocytes of human subjects recently infected with M. tuberculosis, but were not seen in naive control subjects. These results define a new class of broadly distributed lipid antigens presented by the CD1 system during infection in vivo and suggest an immune mechanism for recognition of senescent or transformed cells that are known to have altered dolichol lipids.


Publication metadata

Author(s): Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat J-P, Brenner MB, Costello CE, Besra GS, Porcelli SA

Publication type: Article

Publication status: Published

Journal: Nature

Year: 2000

Volume: 404

Issue: 6780

Pages: 884-888

ISSN (print): 0028-0836

ISSN (electronic): 1476-4687

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/35009119

DOI: 10.1038/35009119

PubMed id: 10786796


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