HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C
HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C
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DOI：
10.1038/35869
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发表时间：
1998-02-19
期刊：
影响因子：
64.8
通讯作者：
McMichael, AJ
中科院分区：
文献类型：
--
作者：
Braud, VM;Allan, DSJ;McMichael, AJ
HLA-E 蛋白是一种非经典主要组织相容性复合体 (MHC) 分子，序列变异性有限。其在细胞表面的表达受到来自其他一些 MHC I 类分子信号序列的肽的结合的调节 (1,2)。在这里，我们报告了 HLA-E 配体的鉴定。我们构建了四聚体 (3)，其中重组 HLA-E 和 β2-微球蛋白用 MHC 前导序列肽重折叠、生物素化并与藻红蛋白标记的 Extravidin 缀合。这种 HLA-E 四聚体与自然杀伤 (NK) 细胞和外周血中的一小部分 T 细胞结合。在转染子上，四聚体与 CD94/NKG2A、CD94/NKGK2B 和 CD94/NKG2C NK 细胞受体结合，但不与 NK 细胞受体 (KIR) 的免疫球蛋白家族结合。 HLA-E 的表面表达足以保护靶细胞免遭 CD94/NKG2A(+) NK 细胞克隆的裂解。 HLA I 类等位基因的一个子集已被证明可以抑制 CD94/NKG2A(+) NK 细胞克隆的杀伤作用(4-6)。只有具有能够上调 HLA-E 表面表达的前导肽的 HLA 等位基因才具有对 NK 细胞介导的裂解的抗性，这意味着它们的作用是由 HLA-E（NK 细胞抑制性受体 CD94/NKG2A 的主要配体）介导的。
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(1,2). Here we report the identification of ligands for HLA-E. We constructed tetramers(3) in which recombinant HLA-E and beta 2-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(4-6). 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.