Abteilung Primatengenetik, Deutsches Primatenzentrum--Leibniz Institut für Primatenforschung, Kellnerweg 4, 37077, Göttingen, Germany.
Immunogenetics. 2010 Mar;62(3):149-58. doi: 10.1007/s00251-010-0424-5. Epub 2010 Feb 12.
The MHC class I gene family of rhesus macaques is characterised by considerable gene duplications. While a HLA-C-orthologous gene is absent, the Mamu-A and in particular the Mamu-B genes have expanded, giving rise to plastic haplotypes with differential gene content. Although some of the rhesus macaque MHC class I genes are known to be associated with susceptibility/resistance to infectious diseases, the functional significance of duplicated Mamu-A and Mamu-B genes and the expression pattern of their encoded proteins are largely unknown. Here, we present data of the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B molecules. We found strong cell surface and low intracellular expression for Mamu-A1, Mamu-A2 and Mamu-A3-encoded molecules as well as for Mamu-B01704, Mamu-B02101, Mamu-B04801, Mamu-B06002 and Mamu-B13401. In contrast, weak cell surface and strong intracellular expression was seen for Mamu-A41403, Mamu-B01202, Mamu-B02804, Mamu-B03002, Mamu-B05704, Mamu-I010201 and Mamu-I0121. The different expression patterns were assigned to the antigen-binding alpha1 and alpha2 domains, suggesting failure of peptide binding is responsible for retaining 'intracellular' Mamu class I molecules in the endoplasmic reticulum. These findings indicate a diverse functional role of the duplicated rhesus macaque MHC class I genes.
恒河猴 MHC I 类基因家族的特点是存在大量基因重复。虽然缺少与 HLA-C 同源的基因,但 Mamu-A 尤其是 Mamu-B 基因发生了扩张,产生了具有不同基因组成的可塑性单倍型。尽管一些恒河猴 MHC I 类基因与传染病的易感性/抗性有关,但重复的 Mamu-A 和 Mamu-B 基因的功能意义及其编码蛋白的表达模式在很大程度上仍是未知的。在这里,我们展示了 AcGFP 标记的 Mamu-A 和 Mamu-B 分子的亚细胞定位数据。我们发现 Mamu-A1、Mamu-A2 和 Mamu-A3 编码的分子以及 Mamu-B01704、Mamu-B02101、Mamu-B04801、Mamu-B06002 和 Mamu-B13401 具有很强的细胞表面表达和低的细胞内表达,而 Mamu-A41403、Mamu-B01202、Mamu-B02804、Mamu-B03002、Mamu-B05704、Mamu-I010201 和 Mamu-I0121 则表现出较弱的细胞表面表达和较强的细胞内表达。不同的表达模式归因于抗原结合的 alpha1 和 alpha2 结构域,表明肽结合的失败导致“细胞内”恒河猴 MHC I 类分子在内质网中保留。这些发现表明重复的恒河猴 MHC I 类基因具有多样化的功能作用。