A molecular basis for NKT cell recognition of CD1d-self-antigen

Immunity. 2011 Mar 25;34(3):315-26. doi: 10.1016/j.immuni.2011.01.013. Epub 2011 Mar 3.


The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3β loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD1d / immunology*
  • Autoantigens*
  • Crystallography, X-Ray
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Multiprotein Complexes
  • Natural Killer T-Cells / immunology*
  • Receptors, Natural Killer Cell / immunology


  • Antigens, CD1d
  • Autoantigens
  • Multiprotein Complexes
  • Receptors, Natural Killer Cell

Associated data

  • PDB/3AU1
  • PDB/3QI9