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

D. Branch Moody, Timo Ulrichs, Walter Mühlecker, David C. Young, Sudagar S. Gurcha, Ethan Grant, Jean Pierre Rosat, Michael B. Brenner, Catherine E. Costello, Gurdyal S. Besra, Steven A. Porcelli

Research output: Contribution to journalArticle

352 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)884-888
Number of pages5
JournalNature
Volume404
Issue number6780
DOIs
StatePublished - Apr 20 2000

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Mycobacterium Infections
Glycolipids
Terpenes
CD1 Antigens
Mycobacterium tuberculosis
T-Lymphocytes
Lipids
Dolichol
Cell Line
Viral Tumor Antigens
Antigen Presentation
Mycobacterium
T-Cell Antigen Receptor
Glycosylation
Cell Wall
Infection
Proteins

ASJC Scopus subject areas

  • General

Cite this

Moody, D. B., Ulrichs, T., Mühlecker, W., Young, D. C., Gurcha, S. S., Grant, E., ... Porcelli, S. A. (2000). CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature, 404(6780), 884-888. https://doi.org/10.1038/35009119

CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. / Moody, D. Branch; Ulrichs, Timo; Mühlecker, Walter; Young, David C.; Gurcha, Sudagar S.; Grant, Ethan; Rosat, Jean Pierre; Brenner, Michael B.; Costello, Catherine E.; Besra, Gurdyal S.; Porcelli, Steven A.

In: Nature, Vol. 404, No. 6780, 20.04.2000, p. 884-888.

Research output: Contribution to journalArticle

Moody, DB, Ulrichs, T, Mühlecker, W, Young, DC, Gurcha, SS, Grant, E, Rosat, JP, Brenner, MB, Costello, CE, Besra, GS & Porcelli, SA 2000, 'CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection', Nature, vol. 404, no. 6780, pp. 884-888. https://doi.org/10.1038/35009119
Moody DB, Ulrichs T, Mühlecker W, Young DC, Gurcha SS, Grant E et al. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000 Apr 20;404(6780):884-888. https://doi.org/10.1038/35009119
Moody, D. Branch ; Ulrichs, Timo ; Mühlecker, Walter ; Young, David C. ; Gurcha, Sudagar S. ; Grant, Ethan ; Rosat, Jean Pierre ; Brenner, Michael B. ; Costello, Catherine E. ; Besra, Gurdyal S. ; Porcelli, Steven A. / CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. In: Nature. 2000 ; Vol. 404, No. 6780. pp. 884-888.
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