Jefferies W A, Rüther U, Wagner E F, Kvist S
Ludwig Institute for Cancer Research, Stockholm, Sweden.
EMBO J. 1988 Nov;7(11):3423-31. doi: 10.1002/j.1460-2075.1988.tb03216.x.
A chimeric H-2Kd/Kk gene, called pC31, contains the extracellular alpha 1 domain of Kd origin whereas the rest of the molecule is of Kk origin. Disruption of the syngeneic alpha 1-alpha 2 structure results in a total abrogation of the function of the C31 protein as a restriction element for H-2Kd and Kk restricted T cells during virus infection. In an attempt to obtain information on the functional polymorphism of MHC class I antigens as restriction elements, we have introduced the pC31 gene into the germ line of C3H/He mice (H-2k). The pC31 gene was transcribed in all tissues examined and the expression pattern paralleled the endogenous H-2Kk gene. However, the mRNA for the transgene was approximately 10-times more abundant, which was reflected in an elevated expression of the C31 protein in transgenic splenocytes. Most of the C31 antigen was found intracellularly. The C31 antigen could condition transgenic cytotoxic T lymphocytes in a specific manner during influenza A virus infection and functioned as the restricting element during T cell lysis of the infected cells. These results suggest that entire exons may be exchanged between MHC class I genes and that this exchange can generate novel and functional restriction elements.
一种嵌合的H-2Kd/Kk基因,称为pC31,其包含Kd来源的细胞外α1结构域,而分子的其余部分则是Kk来源。同基因α1-α2结构的破坏导致C31蛋白作为病毒感染期间H-2Kd和Kk限制性T细胞的限制元件的功能完全丧失。为了获取有关作为限制元件的MHC I类抗原功能多态性的信息,我们已将pC31基因导入C3H/He小鼠(H-2k)的种系中。pC31基因在所有检测的组织中均有转录,且表达模式与内源性H-2Kk基因相似。然而,转基因的mRNA丰度约高10倍,这反映在转基因脾细胞中C31蛋白的表达升高。大多数C31抗原存在于细胞内。在甲型流感病毒感染期间,C31抗原可以以特定方式调节转基因细胞毒性T淋巴细胞,并在感染细胞的T细胞裂解过程中作为限制元件发挥作用。这些结果表明,MHC I类基因之间可能会交换整个外显子,并且这种交换可以产生新的功能性限制元件。