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猪主要组织相容性复合体(MHC)I类分子的多态性及肽结合特异性

Polymorphism and peptide-binding specificities of porcine major histocompatibility complex (MHC) class I molecules.

作者信息

Fan Shuhua, Wang Yongli, Wang Song, Wang Xian, Wu Yanan, Li Zibin, Zhang Nianzhi, Xia Chun

机构信息

Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, PR China; College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, PR China.

College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, PR China.

出版信息

Mol Immunol. 2018 Jan;93:236-245. doi: 10.1016/j.molimm.2017.06.024. Epub 2017 Jul 24.

DOI:10.1016/j.molimm.2017.06.024
PMID:28751109
Abstract

The swine lymphocyte antigen class I (SLA I) is a highly polymorphic gene superfamily that plays an important role in swine anti-viral immune responses. However, an understanding of the highly variable sites and peptide-binding specificities of SLA I molecule is limited. In this study, a total of 27 SLA I alleles were identified from 3 Tibetan wild boars and 3 Heishan pigs. The phylogenetic relationship between the Tibetan wild boar and other breeds was analyzed using bioinformatics methods, and the highly variable sites were noted in the three dimensional structures of SLA I. Peptides from the porcine reproductive and respiratory syndrome virus (PRRSV) and influenza A virus (IAV) were screened with a bioinformatic method and refolding assay in vitro. The superior SLA I molecules, which have the ability to combine with more peptides, were selected from the Tibetan wild boars and Heishan pigs. The results showed that the SLA I of the Tibetan wild boars was not divergent from other pig breeds and that high-variation sites were mostly located in the peptide binding groove (PBG), suggesting that high variation sites could determines the peptide-binding characteristics and would possibly influences peptide-specific CD8 T cell recognition. The SLA I allele SLA-10302 (known as KY113114) of the Tibetan wild boar formed stable complexes with three PRRSV peptides, and the SLA-3hs0202 (KJ555032) from Heishan pigs was able to bind with four IAV peptides. The results from this study may benefit vaccine development and may help control IAV and PRRSV in swine.

摘要

猪淋巴细胞抗原I类(SLA I)是一个高度多态的基因超家族,在猪的抗病毒免疫反应中发挥重要作用。然而,对SLA I分子的高变位点和肽结合特异性的了解有限。在本研究中,从3头藏猪和3头黑山猪中总共鉴定出27个SLA I等位基因。利用生物信息学方法分析了藏猪与其他品种之间的系统发育关系,并在SLA I的三维结构中标记了高变位点。采用生物信息学方法和体外复性试验筛选了猪繁殖与呼吸综合征病毒(PRRSV)和甲型流感病毒(IAV)的肽段。从藏猪和黑山猪中筛选出能够结合更多肽段的优势SLA I分子。结果表明,藏猪的SLA I与其他猪品种没有差异,高变位点大多位于肽结合槽(PBG)中,这表明高变位点可能决定肽结合特性,并可能影响肽特异性CD8 T细胞识别。藏猪的SLA I等位基因SLA-10302(编号为KY113114)与3个PRRSV肽段形成稳定复合物,黑山猪的SLA-3hs0202(KJ555032)能够与4个IAV肽段结合。本研究结果可能有助于疫苗开发,并有助于控制猪的IAV和PRRSV。

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