Barnden M J, Allison J, Heath W R, Carbone F R
Department of Pathology and Immunology, Monash Medical School, Victoria, Australia.
Immunol Cell Biol. 1998 Feb;76(1):34-40. doi: 10.1046/j.1440-1711.1998.00709.x.
We describe the generation of ovalbumin (OVA)-specific, MHC class II-restricted alpha beta T cell receptor (TCR) transgenic mice. Initial attempts at generating these transgenic mice utilized heterologous regulatory elements to drive the expression of cDNA genes encoding the separate alpha- and beta-chains of the TCR. Unexpectedly, T cells bearing the transgenic alpha beta TCR failed to emerge from the thymus in these mice, although the transgenes did modify endogenous TCR expression. However, subsequent modification of the approach which enabled expression of the TCR beta-chain under the control of its natural regulatory elements generated mice whose peripheral T cells expressed the transgenic TCR and were capable of antigen-dependent proliferation. These results show that successful generation of MHC class II-restricted, OVA-specific alpha beta TCR transgenic mice was dependent upon combining cDNA- and genomic DNA-based constructs for expression of the respective alpha- and beta-chains of the TCR.
我们描述了卵清蛋白（OVA）特异性、MHC II类限制性αβT细胞受体（TCR）转基因小鼠的产生过程。最初尝试产生这些转基因小鼠时，利用异源调控元件来驱动编码TCR单独α链和β链的cDNA基因的表达。出乎意料的是，尽管转基因确实改变了内源性TCR的表达，但携带转基因αβTCR的T细胞未能在这些小鼠的胸腺中出现。然而，随后对方法进行了改进，使得TCRβ链能够在其天然调控元件的控制下表达，从而产生了外周T细胞表达转基因TCR且能够进行抗原依赖性增殖的小鼠。这些结果表明，成功产生MHC II类限制性、OVA特异性αβTCR转基因小鼠依赖于将基于cDNA和基因组DNA的构建体相结合，以表达TCR的相应α链和β链。
