T cell receptor recognition of CD1b presenting a mycobacterial glycolipid.
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.
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
Stephanie
S
Gras
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.|Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Ildiko
0000-0002-1446-5701
I
Van Rhijn
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
Adam
A
Shahine
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tan-Yun
TY
Cheng
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Mugdha
M
Bhati
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Li Lynn
LL
Tan
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Hanim
H
Halim
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus and National Jewish Health, Aurora, Colorado, USA.
Kathryn D
KD
Tuttle
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus and National Jewish Health, Aurora, Colorado, USA.
Laurent
L
Gapin
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
Jérôme
J
Le Nours
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
D Branch
DB
Moody
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.|Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
Jamie
J
Rossjohn
D018949:Antigens, CD1 / Q000378:metabolism*; D006017:Glycolipids / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D055985:Latent Tuberculosis / Q000276:immunology*; D015778:Minor Histocompatibility Antigens / Q000378:metabolism; D009168:Mycobacterium phlei; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016929:Rhodococcus equi; D013601:T-Lymphocytes / Q000276:immunology*
D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; C048938:glucose mycolate