GRP94 MEDIATED IMMUNE RESPONSES EVOKED BY CELL DEATH

这些研究的主要目的是阐明GRP94在细胞死亡后引发抗原呈递细胞（APC）介导的细胞免疫应答的能力。GRP94是一种ER（内质网）伴侣蛋白，具有引发针对其来源的癌组织的预防性和免疫应答的能力。为了使GRP94成为刺激宿主先天免疫应答的相关抗原，它必须从受影响的细胞释放，可能是通过细胞死亡的凋亡或坏死模式。为了确定细胞死亡后GRP94的生理和免疫作用，研究将集中在坏死和凋亡期间GRP94的释放及其此后的免疫活性上。 首先，将检查和定量细胞凋亡和坏死期间GRP94释放到细胞外空间中。接下来，通过建立的交叉呈递模型，将测试释放的GRP94引起免疫应答的能力。最后，通过生物化学和显微技术，ER及其内容物的命运将在细胞死亡过程中进行检查。这项研究将为细胞免疫学、癌症生物学和细胞死亡领域之间架起一座桥梁。

The primary goal of these studies is to elucidate the capacity of GRP94 to elicit antigen presenting cell (APC)-mediated cellular immune responses upon cell death. GRP94, an ER (endoplasmic reticulum) chaperone, has the capability of eliciting prophylactic and immunotherapeutic responses against the cancerous tissue from which it was derived. In order for GRP94 to be a pertinent antigen to stimulate the host's innate immune responses it must be released from the affected cells, likely by the apoptotic or necrotic modes of cell death. To determine the physiological and immunological roles of GRP94 upon cell death, studies will focus upon the release of GRP94 during necrosis and apoptosis and its immunological viability thereafter. First, the release of GRP94 into the extracellular space during apoptosis and necrosis will be examined and quantified. Next, through established models of cross presentation, the released GRP94 will be tested for its capability to raise an immune response. Finally, by biochemical and microscopic techniques, the fate of the ER and it's contents will be examined during the processes of cell death. This research will provide a bridge between the fields of cellular immunology, cancer biology and cell death.