Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

Nat Commun. 2016 Feb 15:7:10570. doi: 10.1038/ncomms10570.

Abstract

Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

Publication types

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

MeSH terms

  • Antigens, CD1d / immunology*
  • Crystallography, X-Ray
  • Galactosylceramides / immunology*
  • Gangliosides / immunology
  • Glucosylceramides / immunology
  • Humans
  • Lipids / immunology
  • Molecular Docking Simulation
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Surface Plasmon Resonance

Substances

  • Antigens, CD1d
  • CD1D protein, human
  • Galactosylceramides
  • Gangliosides
  • Glucosylceramides
  • Lipids
  • Receptors, Antigen, T-Cell, alpha-beta
  • alpha-galactosylceramide