Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies
Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies
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DOI：
10.1111/j.1365-2567.2008.03019.x
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发表时间：
2009-05-01
期刊：
影响因子：
6.4
通讯作者：
Moffett, Ashley
中科院分区：
文献类型：
--
作者：
Apps, Richard;Murphy, Shawn P.;Moffett, Ashley
人类滋养层细胞表达一系列不寻常的人类白细胞抗原（HLA）分子，这些分子一直难以定义。经典 HLA-I 类 (HLA-I) 位点之间的密切同源性和极端多态性使得生成位点特异性单克隆抗体 (mAb) 变得困难。定义抗体针对数千种现有 HLA-I 同种异型的反应性的问题常常使得无法确定来自正常远交群体的生物样品中 mAb 结合的 HLA。在这里，我们使用市售的涂有单个 HLA-I 的珠子来通过实验表征 9 种 mAb 对 96 种常见 HLA-I 同种异型的反应性。结合供体 HLA-I 基因分型，我们可以定义正常个体中这些抗体结合的特定 HLA 分子。我们使用这种方法来分析正常妊娠的初级滋养层细胞的 HLA 表达；绒毛膜癌细胞JEG-3和JAR；以及胎盘细胞系 HTR-8/SVneo、Swan-71 和 TEV-1。我们证实，在正常妊娠中，初级绒毛滋养层细胞是HLA缺失的，而绒毛外滋养层细胞表达HLA-C、HLA-G和HLA-E，但不表达HLA-A、HLA-B或HLA-DR分子。肿瘤来源的 JEG-3 和 JAR 细胞分别反映绒毛外和绒毛滋养层 HLA 表型，但体外衍生的胎盘细胞系的 HLA 库并不代表体内滋养层表型。这项研究提出了关于使用胎盘细胞系的有效性的问题，胎盘细胞系目前可用作胎儿滋养层和携带 HLA 分子受体的母体白细胞之间免疫相互作用的模型系统。
Human trophoblast cells express an unusual repertoire of human leucocyte antigen (HLA) molecules which has been difficult to define. Close homology between and extreme polymorphism at the classical HLA class-I (HLA-I) loci has made it difficult to generate locus-specific monoclonal antibodies (mAbs). The problem of defining an antibody's reactivity against the thousands of existing HLA-I allotypes has often made it impossible to determine the HLA bound by a mAb in biological samples from a normal outbred population. Here we have used commercially available beads coated with individual HLA-I to characterize experimentally the reactivity of nine mAb against 96 common HLA-I allotypes. In conjunction with donor HLA-I genotyping, we could then define the specific HLA molecules bound by these antibodies in normal individuals. We used this approach to analyse the HLA expression of primary trophoblast cells from normal pregnancies; the choriocarcinoma cells JEG-3 and JAR; and the placental cell lines HTR-8/SVneo, Swan-71 and TEV-1. We confirm that primary villous trophoblast cells are HLA null whereas extravillous trophoblast cells express HLA-C, HLA-G and HLA-E, but not HLA-A, HLA-B or HLA-DR molecules in normal pregnancy. Tumour-derived JEG-3 and JAR cells reflect extravillous and villous trophoblast HLA phenotypes, respectively, but the HLA repertoire of the in vitro derived placental cell lines is not representative of either in vivo trophoblast phenotype. This study raises questions regarding the validity of using the placental cell lines that are currently available as model systems for immunological interactions between fetal trophoblast and maternal leucocytes bearing receptors for HLA molecules.