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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 and Rossjohn, Jamie 2016. T cell receptor recognition of CD1b presenting a mycobacterial glycolipid. Nature Communications 7 , 13257. 10.1038/ncomms13257

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Publishing Group
ISSN: 2041-1723
Date of First Compliant Deposit: 5 June 2017
Date of Acceptance: 15 September 2016
Last Modified: 09 Jul 2019 16:12
URI: http://orca-mwe.cf.ac.uk/id/eprint/100008

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