Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities.

Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities.
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DOI:
10.1007/s00251-010-0502-8
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发表时间:
2011-05
期刊:
影响因子:
3.2
通讯作者:
Sette, Alessandro
Sette, Alessandro
中科院分区:
医学4区
文献类型:
--
作者:
Southwood, Scott;Solomon, Christopher;Hoof, Ilka;Rudersdorf, Richard;Sidney, John;Peters, Bjoern;Wahl, Angela;Hawkins, Oriana;Hildebrand, William;Mothe, Bianca R.;Sette, Alessandro

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猴免疫缺陷病毒(SIV)感染的印度恒河猴(Macaca mulatta)是HIV感染和AIDS相关研究的最成熟模型,尽管中国起源的猕猴可能是更相关的模型。中国恒河猴主要组织相容性复合体(MHC)的组成和功能的进一步研究将有助于该物种的更大利用。以往的研究表明,中国起源的M。mulatta(Mamu)I类等位基因比它们的印度对应物更具多态性,这可能推断出更能代表人类MHC(人类白细胞抗原(HLA))的模型。此外,中国恒河猴I类等位基因Mamu-A1*02201是迄今为止鉴定的最常见的等位基因,最近已被表征并显示为HLA-B7超型类似物,是人类群体中最常见的超型。在这项研究中,我们的特点是两个额外的等位基因表达频率高,在中国恒河猴,Mamu-A1*02601和Mamu-B*08301。在MHC-肽结合试验的发展及其相关基序的定义,我们揭示,这些Mamu等位基因共享肽结合特性的HLA-A2和HLA-A3超型,分别是下一个最常见的人类超型后HLA-B7。这些数据表明,中国恒河猴可能确实是一个更有代表性的HLA基因多样性和功能的模型相比,印度起源的物种,因此,一个更好的模型研究人类免疫反应。本文的在线版本(doi:10.1007/s 00251 -010-0502-8)包含补充材料,可供授权用户使用。
The Simian immunodeficiency virus (SIV)-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection and AIDS-related research, despite the potential that macaques of Chinese origin is a more relevant model. Ongoing efforts to further characterize the Chinese rhesus macaques’ major histocompatibility complex (MHC) for composition and function should facilitate greater utilization of the species. Previous studies have demonstrated that Chinese-origin M. mulatta (Mamu) class I alleles are more polymorphic than their Indian counterparts, perhaps inferring a model more representative of human MHC, human leukocyte antigen (HLA). Furthermore, the Chinese rhesus macaque class I allele Mamu-A1*02201, the most frequent allele thus far identified, has recently been characterized and shown to be an HLA-B7 supertype analog, the most frequent supertype in human populations. In this study, we have characterized two additional alleles expressed with high frequency in Chinese rhesus macaques, Mamu-A1*02601 and Mamu-B*08301. Upon the development of MHC–peptide-binding assays and definition of their associated motifs, we reveal that these Mamu alleles share peptide-binding characteristics with the HLA-A2 and HLA-A3 supertypes, respectively, the next most frequent human supertypes after HLA-B7. These data suggest that Chinese rhesus macaques may indeed be a more representative model of HLA gene diversity and function as compared to the species of Indian origin and therefore a better model for investigating human immune responses. The online version of this article (doi:10.1007/s00251-010-0502-8) contains supplementary material, which is available to authorized users.
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