Journal article

Human autoreactive T cells recognize CD1b and phospholipids

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

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2016

Abstract

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...

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Grants

Awarded by National Institutes of Health


Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council


Awarded by A*Star/NHMRC


Awarded by Cancer Research UK


Awarded by Medical Research Council


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

This work is supported by the Bill and Melinda Gates Foundation, National Institutes of Health (AI049313, U19 111224), U.K. Medical Research Council, National Health and Medical Research Council of Australia (1013667), Australian Research Council (CE140100011, LE110100106, and FT140100278), an A*Star/NHMRC joint project grant (1056277), a National Health and Medical Research Council of Australia Senior Principal Research Fellowship (1020770, to D.I.G.), and a National Health and Medical Research Council of Australia Fellowship (AF50 to J.R.).