T CELL RESPONSE TO GENETICALLY ENGINEERED AND MATURED DENDRITIC CELLS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。具体目标：1-在群体和克隆水平上对作为原型黑素瘤相关抗原的Mart-1抗原进行CD 4+和CD 8 + T细胞应答的全面分析，所述原型黑素瘤相关抗原通过在“危险”或“组织损伤”的环境中成熟至免疫原性能力的工程化DC体外呈递。 2-确定抗原特异性CD 4 + T细胞促进和增强对Mart-1抗原的CD 8 + T细胞应答（溶细胞或非溶细胞）的诱导的作用和机制。 3-检查“帮助”的分子基础：a. IL-2信息/IL-2 R表达B.细胞因子共同受体yc c.抗凋亡与促凋亡机制4.检查通过用表达EGFP-TAA融合蛋白的VSV假型逆转录载体（Mart-1和法师-1）遗传工程化的DC进行的区室化表位呈递的体外免疫原性，加上：a.细胞内运输信号序列B.细菌免疫刺激序列

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims: 1-Undertake a comprehensive analysis of both CD4+ and CD8+ T-Cell responses at population and clonal levels to the Mart-1 antigen as a prototype melanoma associated antigen presented in vitro through engineered DC matured to immunogenic competence in an environment of "danger" or "tissue damage". 2-Define the role of and the mechanism by which antigen specific CD4+ T-cells facilitatee and amplify the induction of CD8+ T-cell response, cytolytic or non-cytolytic, to the Mart-1 antigen. 3- Examine the molecular basis of "help": a. IL-2 message/IL-2R expression b.cytokine common receptor yc c. anti-apoptotic vs. pro-apoptotic mechanism 4. Examine the in vitro immunogenicity of compartmentalized epitope presentation by DC genetically engineered with VSV pseudotyped retrovector expressing EGFP-TAA fusion protein (Mart-1 and MAGE-1) plus: a. intracellular trafficking signal sequences b. bacterial immunostimulatory sequences (ISS)