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T cell receptor recognition of CD1b presenting a mycobacterial glycolipid.

ABSTRACT: CD1 proteins present microbial lipids to T cells. Germline-encoded mycolyl lipid-reactive (GEM) T cells with conserved ?? 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 ?-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 ?- and ?-chains as tweezers to surround and grip the glucose moiety of GMM, GEM TCRs create a highly specific mechanism for recognizing this mycobacterial glycolipid.

SUBMITTER: Gras S

PROVIDER: S-EPMC5095289 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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T cell receptor recognition of CD1b presenting a mycobacterial glycolipid.

Gras Stephanie S Van Rhijn Ildiko I Shahine Adam A Cheng Tan-Yun TY Bhati Mugdha M Tan Li Lynn LL Halim Hanim H Tuttle Kathryn D KD Gapin Laurent L Le Nours Jérôme J Moody D Branch DB Rossjohn Jamie J

Nature communications 20161027

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 mutagen ...[more]

PMID: 27807341

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