Human autoreactive T cells recognize CD1b and phospholipids

Ildiko Van Rhijn*, Twan Van Berlo, Tamara Hilmenyuk, Tan Yun Cheng, Benjamin J. Wolf, Raju V.V. Tatituri, Adam P. Uldrich, Giorgio Napolitani, Vincenzo Cerundolo, John D. Altman, Peter Willemsen, Shouxiong Huang, Jamie Rossjohn, Gurdyal S. Besra, M.B. Brenner, Dale I. Godfrey, D.B. Moody

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

65 Citations (Scopus)


In contrast with the common detection of T cells that recognize MHC, CD1a, CD1c, or CD1d proteins, CD1b autoreactive T cells have been difficult to isolate in humans. Here we report the development of polyvalent complexes of CD1b proteins and carbohydrate backbones (dextramers) and their use in identifying CD1b autoreactive T cells from human donors. Activation is mediated by αβ T-cell receptors (TCRs) binding to CD1b-phospholipid complexes, which is sufficient to activate autoreactive responses to CD1b-expressing cells. Using mass spectrometry and T-cell responses to scan through the major classes of phospholipids, we identified phosphatidylglycerol (PG) as the immunodominant lipid antigen. T cells did not discriminate the chemical differences that distinguish mammalian PG from bacterial PG. Whereas most models of T-cell recognition emphasize TCR discrimination of differing self and foreign structures, CD1b autoreactive T cells recognize lipids with dual self and foreign origin. PG is rare in the cellular membranes that carry CD1b proteins. However, bacteria and mitochondria are rich in PG, so these data point to a more general mechanism of immune detection of infection- or stressassociated lipids.

Original languageEnglish
Pages (from-to)380-385
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
Publication statusPublished - 2016


  • CD1b
  • Dendritic cell
  • Lipid antigen
  • Self-antigen
  • T cell


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