T cell receptor recognition of CD1b presenting a mycobacterial glycolipid

Stephanie Gras, Ildiko Van Rhijn, Adam Shahine, Tan-Yun Cheng, Mugdha Bhati, Li Lynn Tan, Hanim Halim, Kathryn D. Tuttle, Laurent Gapin, Jerome Le Nours, D Branch Moody, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number13257
Number of pages12
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 27 Oct 2016

Keywords

  • antigen presentation
  • antigen-presenting cells
  • T-cell receptor
  • x-ray crystallography

Cite this

Gras, Stephanie ; Van Rhijn, Ildiko ; Shahine, Adam ; Cheng, Tan-Yun ; Bhati, Mugdha ; Tan, Li Lynn ; Halim, Hanim ; Tuttle, Kathryn D. ; Gapin, Laurent ; Le Nours, Jerome ; Moody, D Branch ; Rossjohn, Jamie. / T cell receptor recognition of CD1b presenting a mycobacterial glycolipid. In: Nature Communications. 2016 ; Vol. 7.
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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.",
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T cell receptor recognition of CD1b presenting a mycobacterial glycolipid. / Gras, Stephanie; Van Rhijn, Ildiko; Shahine, Adam; Cheng, Tan-Yun; Bhati, Mugdha; Tan, Li Lynn; Halim, Hanim; Tuttle, Kathryn D.; Gapin, Laurent; Le Nours, Jerome; Moody, D Branch; Rossjohn, Jamie.

In: Nature Communications, Vol. 7, 13257, 27.10.2016.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gras, Stephanie

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AU - Tan, Li Lynn

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AU - Tuttle, Kathryn D.

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AU - Le Nours, Jerome

AU - Moody, D Branch

AU - Rossjohn, Jamie

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