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 and Steven A. Porcelli
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D. Branch Moody: Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School
Timo Ulrichs: Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School
Walter Mühlecker: Mass Spectrometry Resource, Boston University School of Medicine
David C. Young: Mass Spectrometry Resource, Boston University School of Medicine
Sudagar S. Gurcha: Albert Einstein College of Medicine, Room 416 Forchheimer Building
Ethan Grant: Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School
Jean-Pierre Rosat: Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School
Michael B. Brenner: Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School
Catherine E. Costello: Mass Spectrometry Resource, Boston University School of Medicine
Gurdyal S. Besra: University of Newcastle Upon Tyne
Steven A. Porcelli: Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School

Nature, 2000, vol. 404, issue 6780, 884-888

Abstract: Abstract The discovery of the CD1 antigen presentation pathway has expanded the spectrum of T-cell antigens to include lipids1,2,3,4, 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.

Date: 2000
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DOI: 10.1038/35009119

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