Carretero M, Cantoni C, Bellón T, Bottino C, Biassoni R, Rodríguez A, Pérez-Villar J J, Moretta L, Moretta A, López-Botet M
Servicio de Immunología, Universidad Autónoma de Madrid, Spain.
Eur J Immunol. 1997 Feb;27(2):563-7. doi: 10.1002/eji.1830270230.
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 approximately 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.
CD94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）细胞介导的对不同HLA同种异型的识别。CD94受体的抑制形式最近已被特异性单克隆抗体（mAb）Z199鉴定出来。在此，我们证明抑制性受体实际上是由CD94与C型凝集素超家族的另一个成员NKG2-A分子（分子量约43 kDa）共价结合形成的复合物，并且Z199单克隆抗体特异性识别NKG2-A分子。尽管编码NKG2-A的cDNA已经为人所知数年，但相应的蛋白质及其可能的功能仍未明确。此外，我们表明NKG2-B蛋白是NKG2-A基因的可变剪接产物，也可以与CD94组装。值得注意的是，NKG2-A和NKG2-B蛋白都含有基于免疫受体酪氨酸的抑制基序（ITIM）。这可能为CD94/NKG2-A受体复合物介导的抑制功能提供分子基础。
