CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells

Eur J Immunol. 2019 May;49(5):737-746. doi: 10.1002/eji.201847949. Epub 2019 Mar 20.

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.

Keywords: CD1b; Lyme disease; T cells; antigen specificity; lipid antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • Antigens, Bacterial / immunology
  • Antigens, CD1 / metabolism*
  • Autoantigens / immunology
  • Borrelia burgdorferi / immunology*
  • Cross Reactions / immunology
  • Diglycerides / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Lyme Disease / immunology*
  • Lyme Disease / metabolism*
  • Lyme Disease / microbiology
  • Lymphocyte Activation / immunology
  • Protein Binding
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • 1,2-diacylglycerol
  • Antigens, Bacterial
  • Antigens, CD1
  • Autoantigens
  • CD1b antigen
  • Diglycerides
  • Epitopes, T-Lymphocyte
  • Receptors, Antigen, T-Cell