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频繁表达的中国恒河猴 MHC Ⅰ类分子 Mamu-A1*02601 和 Mamu-B*08301 的功能分析揭示了 HLA-A2 和 HLA-A3 超型特异性。

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.

机构信息

Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

出版信息

Immunogenetics. 2011 May;63(5):275-90. doi: 10.1007/s00251-010-0502-8. Epub 2011 Jan 28.

Abstract

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-A102201, 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-A102601 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.

摘要

恒河猴免疫缺陷病毒(SIV)感染的印度猕猴(Macaca mulatta)是 HIV 感染和艾滋病相关研究中最成熟的模型,尽管来自中国的猕猴具有更大的相关性。目前正在努力进一步描述中国猕猴的主要组织相容性复合体(MHC)的组成和功能,以促进该物种的更大利用。先前的研究表明,中国来源的猕猴(Mamu)I 类等位基因比其印度对应物更具多态性,这可能表明该模型更能代表人类 MHC、人类白细胞抗原(HLA)。此外,中国猕猴 I 类等位基因 Mamu-A102201 是迄今为止鉴定的最常见等位基因,最近已经被鉴定并被证明是 HLA-B7 超型的类似物,在人类中是最常见的超型。在这项研究中,我们还描述了另外两个在表达频率上较高的中国猕猴等位基因 Mamu-A102601 和 Mamu-B*08301。通过 MHC-肽结合测定法的开发和相关基序的定义,我们揭示这些 Mamu 等位基因与 HLA-A2 和 HLA-A3 超型分别具有肽结合特征,这是仅次于 HLA-B7 的人类下一个最常见的超型。这些数据表明,与来自印度的物种相比,中国猕猴可能确实是 HLA 基因多样性和功能的更具代表性的模型,因此是研究人类免疫反应的更好模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6e/3068250/20378488310c/251_2010_502_Fig1_HTML.jpg

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