CD1d-lipid antigen recognition by the γδ TCR

Nat Immunol. 2013 Nov;14(11):1137-45. doi: 10.1038/ni.2713. Epub 2013 Sep 29.


The T cell repertoire comprises αβ and γδ T cell lineages. Although it is established how αβ T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for γδ TCRs. We describe a population of human Vδ1(+) γδ T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a γδ TCR binds CD1d-α-galactosylceramide (α-GalCer). The γδ TCR docked orthogonally, over the A' pocket of CD1d, in which the Vδ1-chain, and in particular the germ line-encoded CDR1δ loop, dominated interactions with CD1d. The TCR γ-chain sat peripherally to the interface, with the CDR3γ loop representing the principal determinant for α-GalCer specificity. Accordingly, we provide insight into how a γδ TCR binds specifically to a lipid-loaded antigen-presenting molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD1d / chemistry*
  • Antigens, CD1d / immunology
  • Binding Sites
  • Databases, Protein
  • Galactosylceramides / chemistry*
  • Galactosylceramides / immunology
  • Humans
  • Molecular Docking Simulation*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell, gamma-delta / chemistry*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*


  • Antigens, CD1d
  • CD1D protein, human
  • Galactosylceramides
  • Receptors, Antigen, T-Cell, gamma-delta
  • alpha-galactosylceramide

Associated data

  • PDB/4LFH
  • PDB/4LHU