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 ORCID: https://orcid.org/0000-0002-2020-7522 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:	05 May 2023 09:28
URI:	https://orca.cardiff.ac.uk/id/eprint/100008

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