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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 stress-associated lipids.

Original publication

DOI

10.1073/pnas.1520947112

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

12/01/2016

Volume

113

Pages

380 - 385

Keywords

CD1b, T cell, dendritic cell, lipid antigen, self-antigen, Antigen-Presenting Cells, Antigens, CD1, HEK293 Cells, Humans, K562 Cells, Lymphocyte Activation, Mass Spectrometry, Phosphatidylglycerols, Phospholipids, T-Lymphocytes, Transfection