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

Immunity. 2013 Dec 12;39(6):1032-42. doi: 10.1016/j.immuni.2013.11.001. Epub 2013 Nov 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, CD1d / chemistry*
  • Antigens, CD1d / metabolism
  • Crystallography, X-Ray
  • Epitopes
  • Humans
  • Jurkat Cells
  • Lipids / immunology*
  • Major Histocompatibility Complex / immunology
  • Models, Molecular*
  • Protein Structure, Quaternary
  • Receptors, Antigen, T-Cell, gamma-delta / chemistry*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Sulfoglycosphingolipids / chemistry
  • Sulfoglycosphingolipids / metabolism
  • T-Lymphocytes / metabolism*


  • Antigens, CD1d
  • Epitopes
  • Lipids
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sulfoglycosphingolipids

Associated data

  • PDB/4MNG
  • PDB/4MNH
  • PDB/4MQ7
  • PDB/4NDM