Nino-Vasquez J J, Vogel D, Rodriguez R, Moreno A, Patarroyo M E, Pluschke G, Daubenberger C A
Instituto de Inmunologia, Hospital San Juan de Dios, Universidad Nacional de Colombia, Santafe de Bogota, DC.
Immunogenetics. 2000 Mar;51(3):219-30. doi: 10.1007/s002510050035.
The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and Plasmodium vivax and has therefore been recommended by the World Health Organization as a model for evaluation of malaria vaccine candidates. We present here a first step in the molecular characterization of the major histocompatibility complex (MHC) class II DRB genes of Aotus nancymaae (owl monkey or night monkey) by nucleotide sequence analysis of the polymorphic exon 2 segments. In a group of 15 nonrelated animals captivated in the wild, 34 MHC DRB alleles could be identified. Six allelic lineages were detected, two of them having human counterparts, while two other lineages have not been described in any other New World monkey species studied. As in the common marmoset, the diversity of DRB alleles appears to have arisen largely by point mutations in the beta-pleated sheets and by frequent exchange of fixed sequence motifs in the alpha-helical portion. Pairs of alleles differing only at amino acid position b86 by an exchange of valine to glycine are present in Aotus, as in humans. Essential amino acid residues contributing to MHC DR peptide binding pockets number 1 and 4 are conserved or semiconserved between HLA-DR and Aona-DRB molecules, indicating a capacity to bind similar peptide repertoires. These results support fully our using Aotus monkeys as an animal model for evaluation of future subunit vaccine candidates.
新大陆灵长类动物南希夜猴(Aotus nancymaae)易感染人类疟原虫恶性疟原虫(Plasmodium falciparum)和间日疟原虫(Plasmodium vivax),因此世界卫生组织推荐将其作为评估疟疾候选疫苗的模型。我们通过对多态性外显子2片段进行核苷酸序列分析,展示了南希夜猴(夜猴或猫头鹰猴)主要组织相容性复合体(MHC)II类DRB基因分子特征的第一步。在一组15只野外捕获的无亲缘关系动物中,可鉴定出34个MHC DRB等位基因。检测到六个等位基因谱系,其中两个有人类对应物,而另外两个谱系在其他已研究的新大陆猴物种中未被描述。与普通狨猴一样,DRB等位基因的多样性似乎主要源于β折叠片中的点突变以及α螺旋部分固定序列基序的频繁交换。与人类一样,夜猴中存在仅在氨基酸位置b86处缬氨酸与甘氨酸交换而不同的等位基因对。在HLA - DR和Aona - DRB分子之间,对MHC DR肽结合口袋1和4有贡献的必需氨基酸残基是保守或半保守的,这表明它们有能力结合相似的肽库。这些结果充分支持我们将夜猴用作评估未来亚单位候选疫苗的动物模型。