一个古老的MHC链接基因编码了一个非重排的鱼抗体,UrIg,与IgG融合
Martin F Flajnik1, Robyn Stanfield2, Elena N Pokidysheva3
1Department of Microbiology and Immunology, University of Maryland, Baltimore, MD.
Journal of immunology (Baltimore, Md. : 1950)
|August 4, 2023
概括
研究人员在软骨鱼中发现了UrIg,这是一种新型基因,它早于对抗原受体的重新排列. 这种在鱼MHC中发现的基因,可能在适应性免疫的进化中起作用.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 脊椎动物 (gnathostomes) 的适应性免疫是由免疫球蛋白 (Ig) 和T细胞受体 (TCR) 基因以及主要基因相容性复合体 (MHC) 的特征.
- 软骨鱼类代表了拥有这些适应性免疫系统标志的最早的脊椎动物.
研究的目的:
- 研究一种非重组抗原受体类基因UrIg的性质和进化意义,该基因在鱼MHC.中被发现.
- 为了确定表达模式,蛋白质结构和elasmobranchs.ch中的UrIg的潜在功能.
主要方法:
- 对基因模型和cDNA进行生物信息分析,以识别UrIg.
- 对UrIg V区域进行分析,以寻找RAG介导的重排的证据.
- 在不同组织 (肝脏,淋巴细胞器官) 中进行表达分析.
- 生产复合UrIg以研究其寡合化.
- 使用抗UrIg单克隆抗体 (mAbs) 进行西式涂抹和免疫组织化学.
主要成果:
- 位于鱼MHC III类区域的UrIg编码了具有V和C域的蛋白质,但缺乏跨膜区域,这表明它不是细胞表面受体.
- 乌里格V区域没有显示RAG介导的重排,表明它早于RAG转子体入侵.
- UrIg基因在弹性支骨中保存,并且进化缓慢,与Ig/TCR基因不同.
- UrIg主要表达在肝脏,而不是二级淋巴细胞组织.
- 再组合UrIg形成二硫化物结合的同位体,在鱼组织和细胞外基质中检测到.
结论:
- UrIg代表了一个古老的V基因,可能早于RAG转位子和Ig/TCR的出现.
- 它的保存性和细胞外存在表明它与传统的抗原受体有着不同的作用,可能是免疫系统进化的原因.
- UrIg与MHC的关联支持有关Ig/TCR在MHC或原MHC中的起源的假设.
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