Crystal structure of Vδ1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human γδ T cells.
The nature of the antigens recognized by γδ T cells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for Vδ1 TCR-expressing γδ T cells, the major γδ lymphocyte population in epithelial tissues. We crystallized a Vδ1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline Vδ1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3δ residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut Vδ1+ γδ T cells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by γδ T cells and reveal the prevalence of lipid recognition by innate-like T cell populations.
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Adrienne M
AM
Luoma
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Caitlin D
CD
Castro
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Toufic
T
Mayassi
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Leslie A
LA
Bembinster
Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China; Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute.
Li
L
Bai
Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute.
Damien
D
Picard
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Brian
B
Anderson
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Louise
L
Scharf
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Jennifer E
JE
Kung
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Leah V
LV
Sibener
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Paul B
PB
Savage
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Bana
B
Jabri
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute.
Albert
A
Bendelac
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: ejadams@uchicago.edu.
Erin J
EJ
Adams
D000818:Animals; D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D000939:Epitopes; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D055610:Antigens, CD1d; D000939:Epitopes; D008055:Lipids; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013433:Sulfoglycosphingolipids