Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
United States Department of Agriculture, Agricultural Research Service, United States Meat Animal Research Center, Clay Center, NE, 68933, USA.
Immunogenetics. 2022 Jun;74(3):347-365. doi: 10.1007/s00251-022-01254-9. Epub 2022 Feb 9.
Workshop cluster 1 (WC1) molecules are part of the scavenger receptor cysteine-rich (SRCR) superfamily and act as hybrid co-receptors for the γδ T cell receptor and as pattern recognition receptors for binding pathogens. These members of the CD163 gene family are expressed on γδ T cells in the blood of ruminants. While the presence of WC1 γδ T cells in the blood of goats has been demonstrated using monoclonal antibodies, there was no information available about the goat WC1 gene family. The caprine WC1 multigenic array was characterized here for number, structure and expression of genes, and similarity to WC1 genes of cattle and among goat breeds. We found sequence for 17 complete WC1 genes and evidence for up to 30 SRCR a1 or d1 domains which represent distinct signature domains for individual genes. This suggests substantially more WC1 genes than in cattle. Moreover, goats had seven different WC1 gene structures of which 4 are unique to goats. Caprine WC1 genes also had multiple transcript splice variants of their intracytoplasmic domains that eliminated tyrosines shown previously to be important for signal transduction. The most distal WC1 SRCR a1 domains were highly conserved among goat breeds, but fewer were conserved between goats and cattle. Since goats have a greater number of WC1 genes and unique WC1 gene structures relative to cattle, goat WC1 molecules may have expanded functions. This finding may impact research on next-generation vaccines designed to stimulate γδ T cells.
工作坊群集 1(WC1)分子是清道夫受体富含半胱氨酸(SRCR)超家族的一部分,作为γδ T 细胞受体的混合共受体,并作为结合病原体的模式识别受体。这些 CD163 基因家族的成员在反刍动物血液中的γδ T 细胞上表达。虽然已经使用单克隆抗体证明了 WC1 γδ T 细胞存在于山羊血液中,但关于山羊 WC1 基因家族的信息尚不清楚。本文对山羊 WC1 多基因簇进行了特征描述,包括基因的数量、结构和表达,以及与牛 WC1 基因和不同山羊品种之间的相似性。我们发现了 17 个完整的 WC1 基因序列,并证明了多达 30 个 SRCR a1 或 d1 结构域的存在,这些结构域代表了不同基因的独特特征域。这表明 WC1 基因的数量明显多于牛。此外,山羊有七种不同的 WC1 基因结构,其中 4 种是山羊特有的。山羊 WC1 基因的细胞内结构域也有多个转录剪接变体,消除了先前证明对信号转导很重要的酪氨酸。最远端的 WC1 SRCR a1 结构域在山羊品种之间高度保守,但在山羊和牛之间保守的较少。由于山羊相对于牛具有更多的 WC1 基因和独特的 WC1 基因结构,因此山羊 WC1 分子可能具有扩展的功能。这一发现可能会影响针对刺激γδ T 细胞的下一代疫苗的研究。
Dev Comp Immunol. 2021-3
Methods Mol Biol. 2022
Immunogenetics. 2021-4
Transbound Emerg Dis. 2019-9-12
Proc Natl Acad Sci U S A. 2018-1-16