Abstract The immunogenic heat shock protein, gp96, binds to CD91 to elite an immune response, characterized by cross-presentation of chaperoned peptides and release of cytokines, including IL-1β. IL-1β is pro-inflammatory cytokine, which is secreted by immune cells upon sensing pathogen associated molecular pattern (PAMP) or damage associated molecular pattern (DAMP). IL-1β is synthesized as a precursor protein, and requires cleavage by Caspase-1 to the matured IL-1β which is released from the cells. Caspase-1 activation requires the inflammasome protein complex. For Inflammasome activation, signal 1 induces pro-inflammatory gene transcription, and signal 2 activates Inflammasome. We have previously shown that gp96 induces NFκB activation and IL-1β secretion via CD91.1 Here we examined the utilization of the inflammasome for IL-1β in this setting. We report that gp96 is able to work as signal 1 to prime production of pro-IL-1β in APCs and in a dose-dependent manner. The kinetics of priming pro-IL-1β differ between gp96 and other PAMPs such as LPS. We will explore the dependence of IL-1β release on the inflammasome.