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鸡 BG 基因,即丁酰膦胆碱基因家族成员,在外周 T 细胞中的功能等位基因。

Functional Alleles of Chicken BG Genes, Members of the Butyrophilin Gene Family, in Peripheral T Cells.

机构信息

Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Pirbright Institute, Compton, United Kingdom.

出版信息

Front Immunol. 2018 May 1;9:930. doi: 10.3389/fimmu.2018.00930. eCollection 2018.

Abstract

γδ T cells recognize a wide variety of ligands in mammals, among them members of the butyrophilin (BTN) family. Nothing is known about γδ T cell ligands in chickens, despite there being many such cells in blood and lymphoid tissues, as well as in mucosal surfaces. The major histocompatibility complex (MHC) of chickens was discovered because of polymorphic BG genes, part of the BTN family. All but two BG genes are located in the BG region, oriented head-to-tail so that unequal crossing-over has led to copy number variation (CNV) as well as hybrid (chimeric) genes, making it difficult to identify true alleles. One approach is to examine BG genes expressed in particular cell types, which likely have the same functions in different BG haplotypes and thus can be considered "functional alleles." We cloned nearly full-length BG transcripts from peripheral T cells of four haplotypes (B2, B15, B19, and B21), and compared them to the BG genes of the B12 haplotype that previously were studied in detail. A dominant BG gene was found in each haplotype, but with significant levels of subdominant transcripts in three haplotypes (B2, B15, and B19). For three haplotypes (B15, B19, and B21), most sequences are closely-related to BG8, BG9, and BG12 from the B12 haplotype. We found that variation in the extracellular immunoglobulin-variable-like (Ig-V) domain is mostly localized to the membrane distal loops but without evidence for selection. However, variation in the cytoplasmic tail composed of many amino acid heptad repeats does appear to be selected (although not obviously localized), consistent with an intriguing clustering of charged and polar residues in an apparent α-helical coiled-coil. By contrast, the dominantly-expressed BG gene in the B2 haplotype is identical to BG13 from the B12 haplotype, and most of the subdominant sequences are from the BG5-BG7-BG11 clade. Moreover, alternative splicing leading to intron read-through results in dramatically truncated cytoplasmic tails, particularly for the dominantly-expressed BG gene of the B2 haplotype. The approach of examining "functional alleles" has yielded interesting data for closely-related genes, but also thrown up unexpected findings for at least one haplotype.

摘要

γδ T 细胞在哺乳动物中识别各种各样的配体,其中包括丁酰膦蛋白(BTN)家族的成员。尽管禽类的血液、淋巴组织和黏膜表面都有许多这样的细胞,但对于禽类的 γδ T 细胞配体却一无所知。禽类的主要组织相容性复合体(MHC)是因为多态性的 BG 基因而被发现的,这些基因属于 BTN 家族的一部分。除了两个 BG 基因之外,所有的 BG 基因都位于 BG 区域,头对头排列,导致不等交换产生了拷贝数变异(CNV)和杂交(嵌合)基因,这使得确定真正的等位基因变得困难。一种方法是检查特定细胞类型中表达的 BG 基因,这些基因在不同的 BG 单倍型中可能具有相同的功能,因此可以被认为是“功能性等位基因”。我们从四个单倍型(B2、B15、B19 和 B21)的外周 T 细胞中克隆了几乎全长的 BG 转录本,并将它们与之前详细研究过的 B12 单倍型的 BG 基因进行了比较。在每个单倍型中都发现了一个优势 BG 基因,但在三个单倍型(B2、B15 和 B19)中都有显著水平的亚优势转录本。对于三个单倍型(B15、B19 和 B21),大多数序列与 B12 单倍型的 BG8、BG9 和 BG12 密切相关。我们发现,细胞外免疫球蛋白可变样(Ig-V)结构域的变异主要局限于膜远侧环,但没有证据表明存在选择。然而,由许多氨基酸七肽重复组成的细胞质尾部的变异似乎确实受到了选择(尽管没有明显的定位),这与在一个明显的α-螺旋卷曲螺旋中带电和极性残基的有趣聚类一致。相比之下,B2 单倍型中优势表达的 BG 基因与 B12 单倍型中的 BG13 相同,大多数亚优势序列来自 BG5-BG7-BG11 分支。此外,导致内含子通读的选择性剪接导致细胞质尾部明显截断,特别是对于 B2 单倍型的优势表达 BG 基因。检查“功能性等位基因”的方法为密切相关的基因提供了有趣的数据,但至少对一个单倍型也提出了意想不到的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25af/5938342/8581c91a5961/fimmu-09-00930-g001.jpg

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