Otting Nel, Heijmans Corrine M C, Noort Riet C, de Groot Natasja G, Doxiadis Gaby G M, van Rood Jon J, Watkins David I, Bontrop Ronald E
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1626-31. doi: 10.1073/pnas.0409084102. Epub 2005 Jan 21.
The highly polymorphic gene products of the classical MHC class I genes in humans (HLA-A, HLA-B, and HLA-C) play a critical role in the immune defense against intracellular infections. Because non-human primates are important models for AIDS vaccine research, rhesus monkeys from a thoroughly pedigreed and serotyped colony were subjected to full-length cDNA analysis of MHC class I gene transcripts. Rhesus macaques express multiple dominant Mamu-A and Mamu-B transcripts (majors) per chromosome, which are characterized by high expression levels. The presence of additional cDNAs with low levels of expression (minors) suggests evidence for transcriptional control of MHC class I genes. Moreover, phylogenetic analyses illustrate that most of the Mamu-A and Mamu-B loci/lineages identified display no or only limited levels of allelic polymorphism. Thus, MHC class I diversity in rhesus macaques is typified by the existence of an unmatched high number of Mamu-A and Mamu-B region configurations that exhibit polymorphism with regard to the number and combination of transcribed loci present per chromosome.
人类经典MHC I类基因(HLA - A、HLA - B和HLA - C)的高度多态性基因产物在针对细胞内感染的免疫防御中发挥关键作用。由于非人灵长类动物是艾滋病疫苗研究的重要模型,对来自一个谱系清晰且经过血清分型的群体的恒河猴进行了MHC I类基因转录本的全长cDNA分析。恒河猴每条染色体表达多个显性的Mamu - A和Mamu - B转录本(主要转录本),其特点是表达水平高。存在表达水平低的其他cDNA(次要转录本)表明有证据支持MHC I类基因的转录调控。此外,系统发育分析表明,所鉴定的大多数Mamu - A和Mamu - B基因座/谱系显示出无或仅有有限水平的等位基因多态性。因此,恒河猴MHC I类多样性的特点是存在数量众多的Mamu - A和Mamu - B区域构型,这些构型在每条染色体上存在的转录基因座的数量和组合方面表现出多态性。