Doxiadis G G, Otting N, de Groot N G, Noort R, Bontrop R E
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
J Immunol. 2000 Mar 15;164(6):3193-9. doi: 10.4049/jimmunol.164.6.3193.
The rhesus macaque is an important model in preclinical transplantation research and for the study of chronic and infectious diseases, and so extensive knowledge of its MHC (MhcMamu) is needed. Nucleotide sequencing of exon 2 allowed the detection of 68 Mamu-DRB alleles. Although most alleles belong to loci/lineages that have human equivalents, identical Mhc-DRB alleles are not shared between humans and rhesus macaques. The number of -DRB genes present per haplotype can vary from two to seven in the rhesus macaque, whereas it ranges from one to four in humans. Within a panel of 210 rhesus macaques, 24 Mamu-DRB region configurations can be distinguished differing in the number and composition of loci. None of the Mamu-DRB region configurations has been described for any other species, and only one of them displays major allelic variation giving rise to a total of 33 Mamu-DRB haplotypes. In the human population, only five HLA-DRB region configurations were defined, which in contrast to the rhesus macaque exhibit extensive allelic polymorphism. In comparison with humans, the unprecedented polymorphism of the Mamu-DRB region configurations may reflect an alternative strategy of this primate species to cope with pathogens. Because of the Mamu-DRB diversity, nonhuman primate colonies used for immunological research should be thoroughly typed to facilitate proper interpretation of results. This approach will minimize as well the number of animals necessary to conduct experiments.
恒河猴是临床前移植研究以及慢性和传染病研究中的重要模型,因此需要对其MHC(MhcMamu)有广泛的了解。外显子2的核苷酸测序检测到68个Mamu-DRB等位基因。虽然大多数等位基因属于在人类中有对应物的基因座/谱系,但人类和恒河猴之间不存在相同的Mhc-DRB等位基因。恒河猴单倍型中存在的-DRB基因数量从两个到七个不等,而人类中则为一个到四个。在一组210只恒河猴中,可以区分出24种Mamu-DRB区域构型,它们在基因座的数量和组成上有所不同。没有任何其他物种具有已描述的Mamu-DRB区域构型,其中只有一种表现出主要的等位基因变异,产生了总共33种Mamu-DRB单倍型。在人类群体中,仅定义了五种HLA-DRB区域构型,与恒河猴不同的是,这些构型表现出广泛的等位基因多态性。与人类相比,Mamu-DRB区域构型前所未有的多态性可能反映了这种灵长类物种应对病原体的另一种策略。由于Mamu-DRB的多样性,用于免疫学研究的非人灵长类动物群体应进行全面分型,以促进对结果的正确解释。这种方法还将尽量减少进行实验所需的动物数量。