Characterization of pig-tailed macaque classical MHC class I genes: Implications for MHC evolution and antigen presentation in macaques
Characterization of pig-tailed macaque classical MHC class I genes: Implications for MHC evolution and antigen presentation in macaques
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DOI：
10.4049/jimmunol.171.2.875
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Martin, MA
中科院分区：
文献类型：
--
作者：
Lafont, BAP;Buckler-White, A;Martin, MA
在慢病毒感染期间，MHC依赖性CD 8（+）T细胞应答与控制病毒复制和减缓疾病进展相关。猪尾猕猴（Macaca nemestrina）和恒河猴（Macaca mulatta），两种非人灵长类动物物种，通常用于模拟HIV感染，可以表现出不同的灵长类动物慢病毒感染后的临床过程。作为评估MHC I类限制性免疫反应对这些感染的作用的第一步，我们克隆并表征了猪尾猕猴的经典MHC I类基因，并确定了19个与恒河猴MHC-A，-B和-I基因同源的MHC I类等位基因（马内）。Mane-A和Mane-B基因座均为重复基因座，未检测到MHC-C基因座。猪尾猕猴和恒河猴MHC-A等位基因形成两组，由14种多态性定义，主要影响其B肽结合口袋。此外，对多个猪尾猴的分析揭示了三种MHC-A单倍型的存在。这些单倍型在各种旧大陆猴中的分布提供了关于非人灵长类动物MHC-A进化的新见解。在恒河猴和猪尾猕猴中对B和F肽结合口袋的检查表明，它们的MHC-B分子向它们各自的CTL呈现很少的共同肽。
MHC-dependent CD8(+) T cell responses have been associated with control of viral replication and slower disease progression during lentiviral infections. Pig-tailed macaques (Macaca nemestrina) and rhesus monkeys (Macaca mulatta), two nonhuman primate species commonly used to model HIV infection, can exhibit distinct clinical courses after infection with different primate lentiviruses. As an initial step in assessing the role of MHC class I restricted immune responses to these infections, we have cloned and characterized classical MHC class I genes of pig-tailed macaques and have identified 19 MHC class I alleles (Mane) orthologous to rhesus macaque MHC-A, -B, and -I genes. Both Mane-A and Mane-B loci were found to be duplicated, and no MHC-C locus was detected. Pig-tailed and rhesus macaque MHC-A alleles form two groups, as defined by 14 polymorphisms affecting mainly their B peptide-binding pockets. Furthermore, an analysis of multiple pig-tailed monkeys revealed the existence of three MHC-A haplotypes. The distribution of these haplotypes in various Old World monkeys provides new insights about MHC-A evolution in nonhuman primates. An examination of B and F peptide-binding pockets in rhesus and pig-tailed macaques suggests that their MHC-B molecules present few common peptides to their respective CTLs.