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最常见的中国恒河猴 MHC Ⅰ类分子与 HLA-B7 超型共享肽结合库。

The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.

机构信息

Department of Biological Sciences, California State University - San Marcos, San Marcos, CA 92096, USA.

出版信息

Immunogenetics. 2010 Jul;62(7):451-64. doi: 10.1007/s00251-010-0450-3. Epub 2010 May 18.

Abstract

Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus macaque potentially being a more relevant model for AIDS outcomes than the Indian rhesus macaque, the Chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility complex (MHC) composition and function, reducing their greater utilization. In this study, we characterized a total of 50 unique Chinese rhesus macaques from several varying origins for their entire MHC class I allele composition and identified a total of 58 unique complete MHC class I sequences. Only nine of the sequences had been associated with Indian rhesus macaques, and 28/58 (48.3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide binding characteristics with the HLA-B7 supertype, the most frequent supertype in human populations. These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques.

摘要

在用于 AIDS 研究的两种恒河猴亚种中,感染猴免疫缺陷病毒的印度恒河猴(Macaca mulatta)是 HIV 感染最成熟的模型,为发病机制提供了深入了解,并为测试新型疫苗提供了系统。尽管中国恒河猴在 AIDS 结果方面可能比印度恒河猴更相关,但中国恒河猴的主要组织相容性复合体(MHC)组成和功能尚未得到很好的描述,这限制了它们的更大应用。在这项研究中,我们对来自不同来源的总共 50 只中国恒河猴进行了 MHC Ⅰ类等位基因组成的全面特征分析,并鉴定了总共 58 个独特的完整 MHC Ⅰ类序列。只有 9 个序列与印度恒河猴有关,而 58 个序列中有 28 个(48.3%)是新的。在所检测到的所有 MHC 等位基因中,我们根据其更高的表达频率,优先选择 Mamu-A1*02201 进行功能特征分析。在开发 MHC/肽结合测定法并定义其相关基序后,我们发现该等位基因与 HLA-B7 超型共享肽结合特征,HLA-B7 超型是人类中最常见的超型。这些研究首次对中国恒河猴 MHC Ⅰ类分子进行了功能特征分析,也是首次对恒河猴 HLA-B7 进行了类比分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6d/2890073/fcdea9c60fa4/251_2010_450_Fig1_HTML.jpg

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