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Analysis of macaque BTN3A genes and transcripts in the extended MHC: conserved orthologs of human γδ T cell modulators.
Immunogenetics ( IF 3.2 ) Pub Date : 2019-08-05 , DOI: 10.1007/s00251-019-01126-9
Nanine de Groot 1 , Rens Groen 1 , Vaneesha Orie 1 , Jesse Bruijnesteijn 1 , Natasja G de Groot 1 , Gaby G M Doxiadis 1 , Ronald E Bontrop 1, 2
Affiliation  

Butyrophilins (BTN), specifically BTN3A, play a central role in the modulation of γδ T cells, which are mainly present in gut and mucosal tissues. BTN3A1 is known, for example, to activate Vγ9Vδ2 T cells by means of a phosphoantigen interaction. In the extended HLA region, three genes are located, designated BTN3A1, BTN3A2 and BTN3A3, which were also defined in rhesus macaques. In contrast to humans, rhesus monkeys have an additional gene, BTN3A3Like, which has the features of a pseudogene. cDNA analysis of 32 Indian rhesus and 16 cynomolgus macaques originating from multiple-generation families revealed that all three genes are oligomorphic, and the deduced amino acids display limited variation. The macaque BTN3A alleles segregated together with MHC alleles, proving their location in the extended (Major Histocompatibility Complex) MHC. BTN3A nearly full-length transcripts of macaques and humans cluster tightly together in the phylogenetic tree, suggesting that the genes represent true orthologs of each other. Despite the limited level of polymorphism, 15 Mamu- and 14 Mafa-BTN3A haplotypes were defined, and, as in humans, all three BTN3A genes are transcribed in PBMCs and colon tissues. In addition to regular full-length transcripts, a high number of various alternative splicing (AS) products were observed for all BTN3A alleles, which may result in different isoforms. The comparable function of certain subsets of γδ T cells in human and non-human primates in concert with high levels of sequence conservation observed for the BTN3A transcripts presents the opportunity to study these not yet well understood molecules in macaques as a model species.

中文翻译:

在扩展的MHC中分析猕猴BTN3A基因和转录本:人类γδT细胞调节剂的保守直向同源物。

酪氨酸蛋白(BTN),特别是BTN3A,在γδT细胞的调节中起着核心作用,γδT细胞主要存在于肠道和粘膜组织中。已知BTN3A1例如通过磷酸抗原相互作用激活Vγ9Vδ2T细胞。在扩展的HLA区域中,定位了三个基因,分别命名为BTN3A1,BTN3A2和BTN3A3,它们也在恒河猴中定义。与人类相反,恒河猴有另一个基因BTN3A3Like,具有假基因的特征。来自多代家族的32种印度恒河猴和16种食蟹猕猴的cDNA分析表明,这三个基因都是寡聚的,推导的氨基酸显示有限的变异。猕猴BTN3A等位基因与MHC等位基因分离,证明了它们在扩展的(主要组织相容性复合体)MHC中的位置。BTN3A猕猴和人类的近全长转录本紧密地聚集在系统发育树中,表明这些基因代表彼此的真实直系同源物。尽管有限的多态性水平,仍然定义了15个Mamu-和14个Mafa-BTN3A单倍型,并且与人类一样,所有三个BTN3A基因都在PBMC和结肠组织中转录。除了常规的全长转录本外,所有BTN3A等位基因均观察到大量的各种可变剪接(AS)产物,这可能导致不同的亚型。人类和非人类灵长类动物中γδT细胞某些子集的可比功能与BTN3A转录本观察到的高水平序列保守性相结合,为研究猕猴中这些尚未被充分理解的分子作为模型物种提供了机会。
更新日期:2019-11-01
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