DISSIMILAR IMMUNOGENICITIES OF ELA AND E7 ONCOPROTEINS

该项目的目的是使用MCA-102模型系统， 阐明E1 A排斥反应的免疫学机制， 而不是表达E7的肿瘤细胞，在遗传上定义了 E1 A是诱导强大的细胞免疫所需的，并且进一步 表征E1 A而不是E7诱导细胞凋亡的分子基础。 在两个特定的目标中的强有力的细胞免疫应答。 具体目标1：阐明参与免疫系统的关键免疫机制。 表达E1 A但不表达E7的肿瘤细胞的排斥。具体来说， 将决定NK细胞，T细胞， 穿孔素和Fas介导的细胞溶解和细胞因子IL-12和IFNg， 对表达E1 A但不表达E7的肿瘤细胞的排斥。 具体目标 2：定义E1 A-p300结合和E1 A-p300结合的分子机制。 外显子2的表达激活NK细胞反应，从而触发 针对表达E1 A的肿瘤细胞的强大细胞免疫应答。

The purpose of the project is to use the MCA-102 model system to elucidate the immunologic mechanisms involved in the rejection of E1A- but not E7-expressing tumor cells, genetically define the components of ElA that are required to induce robust cellular immunity, and further characterize the molecular basis by which ElA but not E7 induces a vigorous cellular immune response in two specific aims. Specific Aim 1: Elucidate the key immunologic mechanisms involved in the rejection of tumor cells expressing ElA but not E7. Specifically they will determine the interrelationship and function of NK cells, T cells, perforin- and Fas-mediated lysis and the cytokines, IL-12 and IFNg, in the rejection of E1A- but not E7-expressing tumor cells. Specific Aim 2: Define the molecular mechanisms by which E1A-p300 binding and ElA- exon 2 expression activate the NK cell response, thereby triggering a robust cellular immune response against E1A-expressing tumor cells.