GRP94 MEDIATED IMMUNE RESPONSES EVOKED BY CELL DEATH

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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.