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

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

DOI: 10.1073/pnas.1520947112

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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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Adam Uldrich Author Microbiology and Immunology

Jamie Rossjohn Author Microbiology and Immunology

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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.).