Evolution of immunogenetic components encoding ultralong CDR H3.
Evolution of immunogenetic components encoding ultralong CDR H3.
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DOI：
10.1007/s00251-023-01305-9
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发表时间：
2023-08
期刊：
影响因子：
3.2
通讯作者：
Criscitiello, Michael F. F.
中科院分区：
文献类型：
--
作者：
Ott, Jeannine A. A.;Mitchell, Christian;Sheppard, Morgan;Deiss, Thad C. C.;Horton, J. M. Cody;Haakenson, Jeremy K. K.;Huang, Ruiqi;Kelley, Abigail R. R.;Davis, Brian W. W.;Derr, James N. N.;Smider, Vaughn V. V.;Criscitiello, Michael F. F.
大多数脊椎动物的基因组在其IG基因座内含有许多V、D和J基因片段，以通过组合多样性构建高度可变的CDR 3序列。这种核苷酸变异性转化为含有广泛互补位多样性的抗体群体。牛具有相对较少的功能性VDJ基因片段，需要创新方法来产生多样性，如使用超长编码IGHV和IGHD基因片段，产生显著延长的CDR H3。独特的球和茎微结构域产生延长的互补位，其中抗原结合球位于长茎的顶部，允许抗体结合表面和凹陷的抗原表位。我们检查了12种牛科动物的基因组，以确定超长编码IGHV和IGHD基因片段进化的时间。我们在6个牛科动物（牛、瘤牛、野牦牛、家牦牛、美洲野牛和家大额牛）的超长IGHV片段中定位了编码独特TTVHQ基序的8-bp重复，但我们没有发现在牛和野牛属以外的物种中重复的证据。此外，我们分析了来自野牛脾脏的mRNA，并鉴定了表达的超长CDR H3抗体mRNA的丰富库，表明野牛在其宿主防御中使用超长IGHV转录物。我们发现超长编码IGHD基因片段在所有相同的物种，除了国内牦牛，但再次没有超出牛和野牛分支。因此，导致这种超长编码IGHV基因片段和超长编码IGHD基因片段的出现的复制事件似乎是在5- 1000万年前在Bos和野牛属的共同祖先中进化的。 在线版本包含补充材料，可通过10.1007/s 00251 -023-01305-9获得。
The genomes of most vertebrates contain many V, D, and J gene segments within their Ig loci to construct highly variable CDR3 sequences through combinatorial diversity. This nucleotide variability translates into an antibody population containing extensive paratope diversity. Cattle have relatively few functional VDJ gene segments, requiring innovative approaches for generating diversity like the use of ultralong-encoding IGHV and IGHD gene segments that yield dramatically elongated CDR H3. Unique knob and stalk microdomains create protracted paratopes, where the antigen-binding knob sits atop a long stalk, allowing the antibody to bind both surface and recessed antigen epitopes. We examined genomes of twelve species of Bovidae to determine when ultralong-encoding IGHV and IGHD gene segments evolved. We located the 8-bp duplication encoding the unique TTVHQ motif in ultralong IGHV segments in six Bovid species (cattle, zebu, wild yak, domestic yak, American bison, and domestic gayal), but we did not find evidence of the duplication in species beyond the Bos and Bison genera. Additionally, we analyzed mRNA from bison spleen and identified a rich repertoire of expressed ultralong CDR H3 antibody mRNA, suggesting that bison use ultralong IGHV transcripts in their host defense. We found ultralong-encoding IGHD gene segments in all the same species except domestic yak, but again not beyond the Bos and Bison clade. Thus, the duplication event leading to this ultralong-encoding IGHV gene segment and the emergence of the ultralong-encoding IGHD gene segment appears to have evolved in a common ancestor of the Bos and Bison genera 5–10 million years ago. The online version contains supplementary material available at 10.1007/s00251-023-01305-9.
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影响因子：
4.8
作者：
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