HLA-DO is an intracellular class II molecule with distinctive thymic expression
HLA-DO is an intracellular class II molecule with distinctive thymic expression
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DOI：
10.1093/intimm/9.3.355
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发表时间：
1997-03-01
影响因子：
4.4
通讯作者：
Altmann, DM
中科院分区：
文献类型：
--
作者：
Douek, DC;Altmann, DM
HLA II 类区域中 HLA-DNA 和 -DOB 基因的状态多年来仍不清楚。在 B 细胞和其他一些细胞类型中可以检测到来自每个基因座的弱 mRNA 转录本，但蛋白质是否产生以及它们是否获得伴侣链以形成 II 类异二聚体的问题尚未解决。同源鼠基因的产物彼此配对形成H-20异二聚体。我们现在报道HLA-DNA 和-DOB 的产物在人类中表达为异源二聚体，即HLA-DO。它在包括树突状细胞在内的各种 II 类阳性细胞中表达。异二聚体与不变链缔合并且具有相对较短的半衰期。其亚细胞分布与 HLA-DR 不同，尽管在一些含有 DR 的区室中发现它，但它不在细胞表面表达，表明其在 II 类功能的细胞内阶段发挥作用。在胸腺中，皮质和髓质的细胞亚群，包括 HLA-DR(+) 和 DR(-) 细胞，都是 HLA-DO+。哈萨尔氏小体是胸腺细胞死亡的髓质部位，周围环绕着 HLA-DO+ 上皮细胞。这种不寻常的表达模式可能表明 HLA-DO 在胸腺中具有特殊的作用。
The status of the HLA-DNA and -DOB genes in the HLA class II region has remained unclear for several years. Weak mRNA transcripts from each locus can be detected in B cells and some other cell types, but the issues of whether proteins are generated and, if so, whether they acquire partner chains to form class II heterodimers have not been resolved. The products of the homologous murine genes pair with each other to form the H-20 heterodimer. We now report that the products of HLA-DNA and -DOB are expressed as a heterodimer in humans, HLA-DO. It is expressed in various class II-positive cells including dendritic cells. The heterodimer associates with invariant chain and has a relatively short half-life. Its subcellular distribution differs from HLA-DR such that it is not expressed at the cell surface although it is found in some DR-containing compartments, suggesting a role at the intracellular stage of class II function. In the thymus, subpopulations of cells in both cortex and medulla, including HLA-DR(+) and DR(-) cells, are HLA-DO+. Hassall's corpuscles, a medullary site of thymocyte death, are ringed by HLA-DO+ epithelium. This unusual pattern of expression may suggest a specialized role for HLA-DO in the thymus.