DISSIMILAR IMMUNOGENICITIES OF ELA AND E7 ONCOPROTEINS

该项目的目的是使用MCA-102模型系统来 阐明E1a排斥反应的免疫学机制 而不是表达E7的肿瘤细胞，从基因上定义了 ELA是诱导强大的细胞免疫所必需的，而且进一步 描述ELA而不是E7诱导的分子基础 强烈的细胞免疫反应有两个特定的目标。 具体目标1：阐明涉及的关键免疫学机制 表达ELA但不表达E7的肿瘤细胞的排斥反应。具体来说，他们 将决定NK细胞、T细胞、 穿孔素和Fas介导的裂解与细胞因子IL-12和IFNG的关系 对表达E1a但不表达E7的肿瘤细胞的排斥反应。特定目标 2：确定E1a-p300结合和Ela- 外显子2的表达激活了NK细胞的反应，从而触发了 针对表达E1a的肿瘤细胞的强大细胞免疫反应。

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.