Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 498431
Title Human autoreactive T cells recognize CD1b and phospholipids
Author(s) Rhijn, Ildiko Van; Berlo, Twan Van; Hilmenyuk, Tamara; Cheng, Tan Yun; Wolf, Benjamin J.; Tatituri, Raju V.V.; Uldrich, Adam P.; Napolitani, Giorgio; Cerundolo, Vincenzo; Altman, John D.; Willemsen, Peter; Huang, Shouxiong; Rossjohn, Jamie; Besra, Gurdyal S.; Brenner, M.B.; Godfrey, Dale I.; Moody, D.B.
Source Proceedings of the National Academy of Sciences of the United States of America 113 (2016)2. - ISSN 0027-8424 - p. 380 - 385.
DOI http://dx.doi.org/10.1073/pnas.1520947112
Department(s) CVI Infection Biology
Publication type Refereed Article in a scientific journal
Publication year 2016
Keyword(s) CD1b - Dendritic cell - Lipid antigen - Self-antigen - T cell
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. 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.

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