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

Author

Listed:
  • Veronique M. Braud

    (Institute of Molecular Medicine, John Radcliffe Hospital)

  • David S. J. Allan

    (Institute of Molecular Medicine, John Radcliffe Hospital)

  • Christopher A. O'Callaghan

    (Institute of Molecular Medicine, John Radcliffe Hospital)

  • Kalle Söderström

    (DNAX Research Institute of Molecular and Cellular Biology)

  • Annalisa D'Andrea

    (DNAX Research Institute of Molecular and Cellular Biology)

  • Graham S. Ogg

    (Institute of Molecular Medicine, John Radcliffe Hospital)

  • Sasha Lazetic

    (DNAX Research Institute of Molecular and Cellular Biology)

  • Neil T. Young

    (John Radcliffe Hospital)

  • John I. Bell

    (Institute of Molecular Medicine, John Radcliffe Hospital)

  • Joseph H. Phillips

    (DNAX Research Institute of Molecular and Cellular Biology)

  • Lewis L. Lanier

    (DNAX Research Institute of Molecular and Cellular Biology)

  • Andrew J. McMichael

    (Institute of Molecular Medicine, John Radcliffe Hospital)

Abstract

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 molecules1,2. Here we report the identification of ligands for HLA-E. We constructed tetramers3 in which recombinant HLA-E and β2-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 clones4,5,6. 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.

Suggested Citation

  • Veronique M. Braud & David S. J. Allan & Christopher A. O'Callaghan & Kalle Söderström & Annalisa D'Andrea & Graham S. Ogg & Sasha Lazetic & Neil T. Young & John I. Bell & Joseph H. Phillips & Lewis L, 1998. "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C," Nature, Nature, vol. 391(6669), pages 795-799, February.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6669:d:10.1038_35869
    DOI: 10.1038/35869
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    Cited by:

    1. Xianke Xiang & Yao He & Zemin Zhang & Xuerui Yang, 2024. "Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Brooke D. Huisman & Ning Guan & Timo Rückert & Lee Garner & Nishant K. Singh & Andrew J. McMichael & Geraldine M. Gillespie & Chiara Romagnani & Michael E. Birnbaum, 2023. "High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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