CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells.
Reinink, Peter Souter, Michael N T Cheng, Tan-Yun van Gorkom, Tamara Lenz, Stefanie Kubler-Kielb, Joanna Strle, Klemen Kremer, Kristin Thijsen, Steven F T Steere, Allen C
Reinink, Peter
Souter, Michael N T
Cheng, Tan-Yun
van Gorkom, Tamara
Lenz, Stefanie
Kubler-Kielb, Joanna
Strle, Klemen
Kremer, Kristin
Thijsen, Steven F T
Steere, Allen C
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Series / Report no.
Open Access
Type
Article
Language
en
Date of publication
2019-03-10
Year of publication
Research Projects
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Journal Issue
Title
CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells.
Translated Title
Published in
Eur J Immunol 2019; 49(5):737-46
Abstract
Lyme disease is a common multisystem disease caused by infection with a tick-transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL-II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL-II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b-BbGL-II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL-II-like molecules using tetramers and activation assays revealed a concomitant response to CD1b-expressing APCs in absence of BbGL-II. Further, among all major classes of self-lipid tested, BbGL-II responsive TCRs show strong cross-reactivity to diacylglycerol, a self-lipid antigen with structural similarities to BbGL-II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross-reactive CD1b-restricted T cell responses to bacterial and self-antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross-reactive T cells.