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T cell receptor recognition of CD1b presenting a mycobacterial glycolipid

Author

Listed:
  • Stephanie Gras

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University
    Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University)

  • Ildiko Van Rhijn

    (Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School
    Faculty of Veterinary Medicine, Utrecht University)

  • Adam Shahine

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University
    Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University)

  • Tan-Yun Cheng

    (Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School)

  • Mugdha Bhati

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University)

  • Li Lynn Tan

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University)

  • Hanim Halim

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University)

  • Kathryn D. Tuttle

    (University of Colorado Anschutz Medical Campus and National Jewish Health)

  • Laurent Gapin

    (University of Colorado Anschutz Medical Campus and National Jewish Health)

  • Jérôme Le Nours

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University
    Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University)

  • D. Branch Moody

    (Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School)

  • Jamie Rossjohn

    (Infection and Immunity Program, Biomedicine Discovery Institute, Monash University
    Monash University
    Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University
    Institute of Infection and Immunity, Cardiff University School of Medicine)

Abstract

CD1 proteins present microbial lipids to T cells. Germline-encoded mycolyl lipid-reactive (GEM) T cells with conserved αβ T cell receptors (TCRs) recognize CD1b presenting mycobacterial mycolates. As the molecular basis underpinning TCR recognition of CD1b remains unknown, here we determine the structure of a GEM TCR bound to CD1b presenting glucose-6-O-monomycolate (GMM). The GEM TCR docks centrally above CD1b, whereby the conserved TCR α-chain extensively contacts CD1b and GMM. Through mutagenesis and study of T cells from tuberculosis patients, we identify a consensus CD1b footprint of TCRs present among GEM T cells. Using both the TCR α- and β-chains as tweezers to surround and grip the glucose moiety of GMM, GEM TCRs create a highly specific mechanism for recognizing this mycobacterial glycolipid.

Suggested Citation

  • Stephanie Gras & Ildiko Van Rhijn & Adam Shahine & Tan-Yun Cheng & Mugdha Bhati & Li Lynn Tan & Hanim Halim & Kathryn D. Tuttle & Laurent Gapin & Jérôme Le Nours & D. Branch Moody & Jamie Rossjohn, 2016. "T cell receptor recognition of CD1b presenting a mycobacterial glycolipid," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13257
    DOI: 10.1038/ncomms13257
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