Urvater J A, Otting N, Loehrke J H, Rudersdorf R, Slukvin I I, Piekarczyk M S, Golos T G, Hughes A L, Bontrop R E, Watkins D I
Wisconsin Regional Primate Research Center, Department of Genetics, University of Wisconsin, Madison, WI 53715, USA.
J Immunol. 2000 Feb 1;164(3):1386-98. doi: 10.4049/jimmunol.164.3.1386.
The rhesus macaque is an important animal model for several human diseases and organ transplantation. Therefore, definition of the MHC of this species is crucial to the development of these models. Unfortunately, unlike humans, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs. From which locus these various alleles are derived is unclear. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MHC class I locus, Mamu-I. We isolated 26 I locus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recent duplication of the B locus occurring after the divergence of macaques from the ancestor of the other extant Cercopithecine genera. Mamu-I mRNA transcripts were detected in all tissues examined and Mamu-I protein was produced in rhesus B lymphoblastoid cell lines. Furthermore, Mamu-I protein was detected by flow cytometry on the surface of human 721.221 cells transfected with Mamu-I. In contrast to the polymorphism present at this locus, there is unusually low sequence variability, with the mean number of nucleotide differences between alleles being only 3.6 nt. Therefore, Mamu-I is less variable than any other polymorphic MHC class I locus described to date. Additionally, no evidence for positive selection on the peptide binding region was observed. Together, these results suggest that Mamu-I is an MHC class I locus in primates that has features of both classical and nonclassical loci.
恒河猴是多种人类疾病和器官移植的重要动物模型。因此，明确该物种的主要组织相容性复合体（MHC）对于这些模型的开发至关重要。不幸的是，与人类不同，来自单个恒河猴的淋巴细胞可表达多达12种不同的MHC I类cDNA。目前尚不清楚这些不同的等位基因源自哪个基因座。在我们试图明确恒河猴MHC I类基因座的过程中，我们鉴定出了一个不寻常的MHC I类基因座，即Mamu-I。我们从三种不同的猕猴物种中分离出了26个I类基因座等位基因，但在其他三个猕猴属中未分离到，这表明I类基因座是猕猴从其他现存猕猴属的祖先分化后B类基因座近期发生重复的结果。在所有检测的组织中均检测到了Mamu-I mRNA转录本，并且在恒河猴B淋巴母细胞系中产生了Mamu-I蛋白。此外，通过流式细胞术在转染了Mamu-I的人721.221细胞表面检测到了Mamu-I蛋白。与该基因座存在的多态性相反，其序列变异性异常低，等位基因之间的核苷酸差异平均数仅为3.6个核苷酸。因此，Mamu-I的变异性低于迄今为止描述的任何其他多态性MHC I类基因座。此外，未观察到肽结合区域存在正选择的证据。综上所述，这些结果表明Mamu-I是灵长类动物中的一个MHC I类基因座，具有经典和非经典基因座的特征。
