HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C

V M Braud, David S J Allan, C A O'Callaghan, K Söderström, A D'Andrea, G S Ogg, S Lazetic, Neil Thomas Young, J I Bell, J H Phillips, L L Lanier, A J McMichael

Research output: Contribution to journalArticlepeer-review

1825 Citations (Scopus)


The protein HLA-E is a non-classical major histocompatibility complex (MHC) molecule of limited sequence variability. Its expression on the cell surface is regulated by the binding of peptides derived from the signal sequence of some other MHC class I molecules. Here we report the identification of ligands for HLA-E. We constructed tetramers in which recombinant HLA-E and beta2-microglobulin were refolded with an MHC leader-sequence peptide, biotinylated, and conjugated to phycoerythrin-labelled Extravidin. This HLA-E tetramer bound to natural killer (NK) cells and a small subset of T cells from peripheral blood. On transfectants, the tetramer bound to the CD94/NKG2A, CD94/NKGK2B and CD94/NKG2C NK cell receptors, but did not bind to the immunoglobulin family of NK cell receptors (KIR). Surface expression of HLA-E was enough to protect target cells from lysis by CD94/NKG2A+ NK-cell clones. A subset of HLA class I alleles has been shown to inhibit killing by CD94/NKG2A+ NK-cell clones. Only the HLA alleles that possess a leader peptide capable of upregulating HLA-E surface expression confer resistance to NK-cell-mediated lysis, implying that their action is mediated by HLA-E, the predominant ligand for the NK cell inhibitory receptor CD94/NKG2A.
Original languageEnglish
Pages (from-to)795-799
Number of pages5
Issue number6669
Publication statusPublished - 19 Feb 1998


  • Animals
  • Antigens, CD
  • Cell Line
  • Cloning, Molecular
  • Cytotoxicity, Immunologic
  • Escherichia coli
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Humans
  • Killer Cells, Natural
  • Lectins, C-Type
  • Ligands
  • Membrane Glycoproteins
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Protein Binding
  • Protein Sorting Signals
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, Natural Killer Cell
  • Recombinant Proteins
  • Transfection
  • beta 2-Microglobulin


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