The Pirbright Institute, Woking, Surrey GU24 0NF, United Kingdom.
The Pirbright Institute, Woking, Surrey GU24 0NF, United Kingdom
J Immunol. 2020 May 1;204(9):2455-2463. doi: 10.4049/jimmunol.1801363. Epub 2020 Mar 25.
Cattle possess the most diverse repertoire of NK cell receptor genes among all mammals studied to date. Killer cell receptor genes encoded within the NK complex and killer cell Ig-like receptor genes encoded within the leukocyte receptor complex have both been expanded and diversified. Our previous studies identified two divergent and polymorphic alleles within the NK complex in the Holstein-Friesian breed of dairy cattle. By examining a much larger cohort and other ruminant species, we demonstrate the emergence and fixation of two allele lineages ( and -) at a single locus during ruminant speciation. Subsequent recombination events between these allele lineages have increased the frequency of extracellular domains. and transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of , regardless of the allele lineage. mRNA levels were also generally higher than Collectively, these data point toward alternative functional roles governed by genotype and allele lineage. On a background of high genetic diversity of NK cell receptor genes, this allele fixation points to fundamental and potentially differential function roles.
牛在所有已研究的哺乳动物中拥有最多样化的 NK 细胞受体基因库。在 NK 复合体中编码的杀伤细胞受体基因和在白细胞受体复合体中编码的杀伤细胞免疫球蛋白样受体基因都已经扩展和多样化。我们之前的研究在荷斯坦-弗里森奶牛品种的 NK 复合体中发现了两个不同的多态性 等位基因。通过检查一个更大的队列和其他反刍动物物种,我们证明了在反刍动物物种形成过程中,单一基因座上的两个 等位基因谱系(和 -)的出现和固定。这些等位基因谱系之间的随后重组事件增加了 细胞外结构域的频率。 和 的转录水平对细胞因子刺激有反应,而无论等位基因谱系如何,纯合动物始终转录更高水平的 。 的 mRNA 水平通常也高于 。总的来说,这些数据表明由 基因型和等位基因谱系控制的替代功能作用。在 NK 细胞受体基因高度遗传多样性的背景下,这个 等位基因固定指向基本的和潜在的不同功能作用。