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; Jérôme Le Nours; D Branch Moody; Jamie Rossjohn

doi:10.1038/ncomms13257

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, Jérôme Le Nours, D Branch Moody, Jamie Rossjohn

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Article number	13257
Journal	Nature Communications [E]
Volume	7
DOIs	https://doi.org/10.1038/ncomms13257
Publication status	Published - 2016

Keywords

Antigen presentation
Antigen-presenting cells
T-cell receptor
X-ray crystallography

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms13257

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@article{7d8e1864759445e8b7d6f13b2c08cfcf,

title = "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 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.",

keywords = "Antigen presentation, Antigen-presenting cells, T-cell receptor, X-ray crystallography",

author = "Stephanie Gras and \{Van Rhijn\}, Ildiko and Adam Shahine and Tan-Yun Cheng and Mugdha Bhati and Tan, \{Li Lynn\} and Hanim Halim and Tuttle, \{Kathryn D\} and Laurent Gapin and \{Le Nours\}, J{\'e}r{\^o}me and Moody, \{D Branch\} and Jamie Rossjohn",

year = "2016",

doi = "10.1038/ncomms13257",

language = "English",

volume = "7",

journal = "Nature Communications [E]",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - T cell receptor recognition of CD1b presenting a mycobacterial glycolipid

AU - Gras, Stephanie

AU - Van Rhijn, Ildiko

AU - Shahine, Adam

AU - Cheng, Tan-Yun

AU - Bhati, Mugdha

AU - Tan, Li Lynn

AU - Halim, Hanim

AU - Tuttle, Kathryn D

AU - Gapin, Laurent

AU - Le Nours, Jérôme

AU - Moody, D Branch

AU - Rossjohn, Jamie

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Antigen presentation

KW - Antigen-presenting cells

KW - T-cell receptor

KW - X-ray crystallography

U2 - 10.1038/ncomms13257

DO - 10.1038/ncomms13257

M3 - Article

C2 - 27807341

SN - 2041-1723

VL - 7

JO - Nature Communications [E]

JF - Nature Communications [E]

M1 - 13257

ER -

T cell receptor recognition of CD1b presenting a mycobacterial glycolipid

Abstract

Keywords

UN SDGs

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