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

26 Citations (Scopus)

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

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