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与CD94复合的NKG2A定义了一种新型抑制性自然杀伤细胞受体。

NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor.

作者信息

Brooks A G, Posch P E, Scorzelli C J, Borrego F, Coligan J E

机构信息

Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.

出版信息

J Exp Med. 1997 Feb 17;185(4):795-800. doi: 10.1084/jem.185.4.795.

DOI:10.1084/jem.185.4.795
PMID:9034158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2196137/
Abstract

CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor for human leukocyte antigen class I molecules. CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on the surface of NK cells. Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94. Analysis of NK cell clones showed that NKG2A was expressed in all NK cell clones whose CD16-dependent killing was inhibited by cross-linking CD94. The induction of an inhibitory signal is consistent with the presence of two immunoreceptor tyrosine-based inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells.

摘要

CD94是一种由自然杀伤(NK)细胞和一部分T细胞表达的C型凝集素。使用抗CD94单克隆抗体进行的阻断研究表明,它是人类白细胞抗原I类分子的受体。最近研究显示CD94是一种与未鉴定的43-kD蛋白共价结合的26-kD蛋白。本报告表明,43-kD蛋白NKG2A在NK细胞表面与CD94共价结合。NKG2A的细胞表面表达依赖于与CD94的结合,因为仅在与CD94结合的NKG2A中发现了成熟蛋白特有的糖基化模式。对NK细胞克隆的分析表明,在所有其依赖CD16的杀伤作用因交联CD94而受到抑制的NK细胞克隆中均表达NKG2A。抑制信号的诱导与NKG2A胞质结构域上存在两个基于免疫受体酪氨酸的抑制基序(V/LXYXXL)一致。在Ly49和杀伤细胞抑制受体上也发现了类似的基序,它们也向NK细胞传递负信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/d64f438befb0/JEM.brooks4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/53e1beef72b9/JEM.brooks1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/8583c7ee5192/JEM.brooks3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/7c5c534ad794/JEM.brooks2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/d64f438befb0/JEM.brooks4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/53e1beef72b9/JEM.brooks1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/8583c7ee5192/JEM.brooks3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/7c5c534ad794/JEM.brooks2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bda/2196137/d64f438befb0/JEM.brooks4.jpg

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J Immunol. 1996 Oct 1;157(7):2804-12.
2
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Immunity. 1996 Aug;5(2):163-72. doi: 10.1016/s1074-7613(00)80492-6.
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Intracellular checkpoints for NK cell cancer immunotherapy.NK 细胞癌症免疫疗法的细胞内检查点。
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