HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer

Eur J Immunol. 1998 Sep;28(9):2854-63. doi: 10.1002/(SICI)1521-4141(199809)28:09<2854::AID-IMMU2854>3.0.CO;2-W.


The HLA-E class Ib molecule constitutes a major ligand for the lectin-like CD94/NKG2 natural killer (NK) cell receptors. Specific HLA class I leader sequence-derived nonapeptides bind to endogenous HLA-E molecules in the HLA-defective cell line 721.221, inducing HLA-E surface expression, and promote CD94/NKG2A-mediated recognition. We compared the ability of NK clones which expressed either inhibitory or activating CD94/NKG2 receptors to recognize HLA-E molecules on the surface of 721.221 cells loaded with a panel of synthetic nonamers derived from the leader sequences of most HLA class I molecules. Our results support the notion that the primary structure of the HLA-E-bound peptides influences CD94/ NKG2-mediated recognition, beyond their ability to stabilize surface HLA-E. Further, CD94/ NKG2A+ NK clones appeared more sensitive to the interaction with most HLA-E-peptide complexes than did effector cells expressing the activating CD94/NKG2C receptor. However, a significant exception to this pattern was HLA-E loaded with the HLA-G-derived nonamer. This complex triggered cytotoxicity very efficiently over a wide range of peptide concentrations, suggesting that the HLA-E/G-nonamer complex interacts with the CD94/NKG2 triggering receptor with a significantly higher affinity. These results raise the possibility that CD94/NKG2-mediated recognition of HLA-E expressed on extravillous cytotrophoblasts plays an important role in maternal-fetal cellular interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic*
  • HLA Antigens / immunology*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type*
  • Ligands
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / immunology*
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptides / immunology
  • Signal Transduction / immunology


  • Antigens, CD
  • HLA Antigens
  • HLA-E antigen
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • KLRD1 protein, human
  • Lectins, C-Type
  • Ligands
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptides