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

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 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.

journal_name

Nature

journal_title

Nature

authors

Braud VM,Allan DS,O'Callaghan CA,Söderström K,D'Andrea A,Ogg GS,Lazetic S,Young NT,Bell JI,Phillips JH,Lanier LL,McMichael AJ

doi

10.1038/35869

subject

Has Abstract

pub_date

1998-02-19 00:00:00

pages

795-9

issue

6669

eissn

0028-0836

issn

1476-4687

journal_volume

391

pub_type

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