Somatic diversification of a transgenic TCR to enhance antiviral immunity and prevent immunopathology (P16)

在淋巴细胞减少的宿主中，病原体清除受损可导致免疫系统的慢性激活。我们打算研究使用基于CRISPR/Cas系统的RNA引导的DNA内切酶作为实现转基因TCR人工体细胞多样化的一种手段。我们将研究在MHC II的背景下呈现的针对LCMV编码抗原肽的TCR的这种体细胞多样化是否导致出现能够控制LCMV感染和防止CD4+细胞介导的免疫病理的不同的CD4+和CD8+T细胞。

An impaired pathogen clearance in lymphopenic hosts can lead to chronic activation of the immune system. We intend to investigate the use of RNA-guided DNA endonucleases based on the CRISPR/Cas system as a means to achieve artificial somatic diversification of a transgenic TCR. We will examine whether such somatic diversification of a TCR that is specific for an LCMV-encoded antigenic peptide presented in the context of MHC II results in the emergence of a diverse repertoire of CD4+ and CD8+ T cells, capable of controlling LCMV infection and preventing CD4+ cell-mediated immunopathology.