Background Recent studies have suggested that mature T cells can change their specificity through reexpression of recombination-activating genes （RAG） and RAG-mediated V（D）J recombination. This process is named re...Background Recent studies have suggested that mature T cells can change their specificity through reexpression of recombination-activating genes （RAG） and RAG-mediated V（D）J recombination. This process is named receptor revision and has been observed in mature peripheral T cells from transgenic mice and human donors. However, whether the receptor revision in mature T cells is a random or orientated process remains poorly understood. Here we used the Jurkat human T cell line, which represents a mature stage of T cell development, as a model to investigate the regulation of T cell receptor （TCR） gene recombination. Methods TCR Dβ-Jβ signal joint T cell receptor excision DNA circles （sjTRECs） were determined by nested and seminested PCR. Double-strand DNA breaks at recombination signal sequences （RSSs） in the TCRVβ chain locus were detected by ligation-mediated-PCR. Further analysis of the complementarity-determining region 3 （CDR3） size of the TCRVβ chain was examined by the TCR GeneScan technique. Results RAG1, RAG2, and three crucial components of the nonhomologous DNA end-joining （NHEJ） pathway were readily detected in Jurkat. Characteristics of junctional diversity of Dβ2-Jβ2 signal joints and ds RSS breaks associated with the Dβ2 5＇ and Dβ 2 3＇ sites were detected in DNA from Jurkat cells. CDR3 size and the gene sequences of the TCRVβ chain did not change during cell proliferation. Conclusions RAG1 and RAG2 and ongoing TCR gene recombination are coexpressed in Jurkat cells, but the ongoing recombination process may not play a role in modification of the TCR repertoire.However, the results suggest that Jurkat could be used as a model for studying the regulation of RAGs and V（D）J recombination and as a ＂special＂ model of the coexistence of TCR gene rearrangements and ＂negative＂ receptor revision.展开更多
被广泛采用的人工免疫系统模型ARTIS中的检测器没有主动学习能力,在具体应用中存在检测半径设定困难、检测性能低等问题,受生物免疫中受体编辑和免疫抑制的启发,提出了一种新的人工免疫系统模型REISAIS(Receptor Editing and Immune Sup...被广泛采用的人工免疫系统模型ARTIS中的检测器没有主动学习能力,在具体应用中存在检测半径设定困难、检测性能低等问题,受生物免疫中受体编辑和免疫抑制的启发,提出了一种新的人工免疫系统模型REISAIS(Receptor Editing and Immune Suppression based Artificial Immune System),模型通过受体编辑分别在耐受期和成熟期赋予检测器一定的主动学习能力,从而提高了模型的检测率,而免疫抑制机制的引入则使得模型的误报率得到了有效控制。给出了模型中检测器和抑制器演化过程的形式化描述,对模型性能进行了分析,证明了受体编辑机制的引入在提高模型检测性能上的有效性。理论分析以及实验结果显示,与ARTIS模型相比,REISAIS模型无需设定检测半径并且检测性能更好。展开更多
基金grants from Major State Basic Research Development 973 Program of China(No.2001CB510008 and 2003CB514113)NSFC & Research Grant Coancil of Hong Kong Joint Research Fund(No.30418003).
文摘Background Recent studies have suggested that mature T cells can change their specificity through reexpression of recombination-activating genes （RAG） and RAG-mediated V（D）J recombination. This process is named receptor revision and has been observed in mature peripheral T cells from transgenic mice and human donors. However, whether the receptor revision in mature T cells is a random or orientated process remains poorly understood. Here we used the Jurkat human T cell line, which represents a mature stage of T cell development, as a model to investigate the regulation of T cell receptor （TCR） gene recombination. Methods TCR Dβ-Jβ signal joint T cell receptor excision DNA circles （sjTRECs） were determined by nested and seminested PCR. Double-strand DNA breaks at recombination signal sequences （RSSs） in the TCRVβ chain locus were detected by ligation-mediated-PCR. Further analysis of the complementarity-determining region 3 （CDR3） size of the TCRVβ chain was examined by the TCR GeneScan technique. Results RAG1, RAG2, and three crucial components of the nonhomologous DNA end-joining （NHEJ） pathway were readily detected in Jurkat. Characteristics of junctional diversity of Dβ2-Jβ2 signal joints and ds RSS breaks associated with the Dβ2 5＇ and Dβ 2 3＇ sites were detected in DNA from Jurkat cells. CDR3 size and the gene sequences of the TCRVβ chain did not change during cell proliferation. Conclusions RAG1 and RAG2 and ongoing TCR gene recombination are coexpressed in Jurkat cells, but the ongoing recombination process may not play a role in modification of the TCR repertoire.However, the results suggest that Jurkat could be used as a model for studying the regulation of RAGs and V（D）J recombination and as a ＂special＂ model of the coexistence of TCR gene rearrangements and ＂negative＂ receptor revision.
文摘被广泛采用的人工免疫系统模型ARTIS中的检测器没有主动学习能力,在具体应用中存在检测半径设定困难、检测性能低等问题,受生物免疫中受体编辑和免疫抑制的启发,提出了一种新的人工免疫系统模型REISAIS(Receptor Editing and Immune Suppression based Artificial Immune System),模型通过受体编辑分别在耐受期和成熟期赋予检测器一定的主动学习能力,从而提高了模型的检测率,而免疫抑制机制的引入则使得模型的误报率得到了有效控制。给出了模型中检测器和抑制器演化过程的形式化描述,对模型性能进行了分析,证明了受体编辑机制的引入在提高模型检测性能上的有效性。理论分析以及实验结果显示,与ARTIS模型相比,REISAIS模型无需设定检测半径并且检测性能更好。
