GRP94 MEDIATED IMMUNE RESPONSES EVOKED BY CELL DEATH

这些研究的主要目的是阐明GRP94在细胞死亡时引发抗原提呈细胞（APC）介导的细胞免疫反应的能力。GRP94是一种内质网伴侣，能够引发针对癌组织的预防和免疫治疗反应。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中释放出来，可能是通过细胞死亡的凋亡或坏死模式。为了确定GRP94在细胞死亡中的生理和免疫学作用，我们将重点研究GRP94在坏死和凋亡过程中的释放及其免疫活性。

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.