The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules

The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules
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DOI:
10.1002/eji.1830270230
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发表时间:
1997-02-01
影响因子:
5.4
通讯作者:
LopezBotet, M
LopezBotet, M
中科院分区:
医学3区
文献类型:
--
作者:
Carretero, M;Cantoni, C;LopezBotet, M

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CD 94是一种含有C型凝集素结构域的II型膜蛋白,已被证明参与自然杀伤(NK)细胞介导的不同HLA同种异型的识别。CD 94受体的抑制形式最近已通过特异性单克隆抗体(mAb)Z199鉴定。在本文中,我们证明抑制性受体实际上是由CD 94与NKG 2-A分子(Mr类似于43 kDa)(C型凝集素超家族的另一个成员)共价结合形成的复合物,并且Z199 mAb特异性识别NKG 2-A分子。虽然编码NKG 2-A的cDNA已经被发现了好几年,但相应的蛋白质及其可能的功能仍然不确定。此外,我们表明,NKG 2-A基因的选择性剪接产物NKG 2-B蛋白也可以与CD 94组装。值得注意的是,NKG 2-A和NKG 2-B蛋白均含有基于细胞质免疫受体酪氨酸的抑制基序(ITIM)。这可能为CD 94/NKG 2-A受体复合物介导的抑制功能提供了分子基础。
CD94, a type II membrane protein containing a C-type lectin domain, has been shown to be involved in natural killer (NK) cell-mediated recognition of different HLA allotypes. The inhibitory form of the CD94 receptor has recently been identified by the specific monoclonal antibody (mAb) Z199. Herein, we demonstrate that the inhibitory receptor is in fact a complex formed by the covalent association of CD94 with the NKG2-A molecule (Mr similar to 43 kDa), another member of the C-type lectin superfamily, and that Z199 mAb specifically recognize NKG2-A molecules. Although the NKG2-A-encoding cDNA has been known for several years, the corresponding protein and its possible function remained undefined. Moreover, we show that the NKG2-B protein, an alternatively spliced product of the NKG2-A gene, can also assemble with CD94. Remarkably, both NKG2-A and NKG2-B proteins contain cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM). This may provide the molecular basis of the inhibitory function mediated by the CD94/NKG2-A receptor complexes.