Polymorphism and peptide-binding specificities of porcine major histocompatibility complex (MHC) class I molecules
Polymorphism and peptide-binding specificities of porcine major histocompatibility complex (MHC) class I molecules
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DOI：
10.1016/j.molimm.2017.06.024
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Xia, Chun
中科院分区：
文献类型：
--
作者：
Fan, Shuhua;Wang, Yongli;Xia, Chun
猪淋巴细胞抗原I类（SLA I）是一个高度多态性的基因超家族，在猪抗病毒免疫应答中起着重要作用。然而，对SLA I分子的高度可变位点和肽结合特异性的理解是有限的。本研究从3头藏野猪和3头黑山猪中共检测到27个SLA I等位基因。利用生物信息学方法分析了藏野猪与其他猪种的系统发育关系，并在SLA I基因的三维结构中发现了高度变异的位点。采用生物信息学方法和体外复性实验对猪繁殖与呼吸综合征病毒（PRRSV）和甲型流感病毒（IAV）的多肽进行了筛选。从藏野猪和黑山猪中筛选出与更多肽段具有联合收割机结合能力的上级SLA I分子。结果表明，藏野猪的SLA I与其它猪种没有差异，高变异位点主要位于肽结合沟（PBG），提示高变异位点决定了肽结合特性，并可能影响肽特异性CD 8（+）T细胞识别。藏野猪的SLA I等位基因SLA-1*0302（KY 113114）能与PRRSV的3个多肽形成稳定的复合物，黑山猪的SLA-3* hs 0202（KJ 555032）能与IAV的4个多肽结合。本研究的结果可能有助于疫苗的开发，并可能有助于控制猪的IAV和PRRSV。
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-1*0302 (known as KY113114) of the Tibetan wild boar formed stable complexes with three PRRSV peptides, and the SLA-3*hs0202 (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.