The immunogenic HSPs are intracellular chaperones of peptides. When HSPs are released from cells they interact with the receptor CD91 on the surface of antigen presenting cells. This allows for cross-presentation of the chaperoned peptides and initiation of various signaling pathways. We have shown that low or high dose gp96 immunization of mice leads to priming of TH1 and Treg responses respectively. Although the mechanisms driving this switch remain largely unknown, these responses have been harnessed for immunotherapy of cancer and autoimmune disease. Our preliminary studies have indicated changes in accumulation and/or recruitment of multiple immune cell subsets in the draining lymph nodes and spleens of mice following immunization with gp96. We propose that such regulation is controlled by DNA methylation states in CD91+ cells. Using next generation sequencing, we have identified these modifications following gp96 immunization. Methyl-seq analysis of CD91+ cells derived from mice immunized with low or high doses of gp96 reveals differential methylation across at least 80 promoter regions, including genes involved in chemotaxis, signaling, and cytokine response. Further exploration will determine which, if any, of these regions are associated with gene silencing. Importantly, these studies show an early requirement for epigenetic changes in response to gp96 and will provide further understanding of the APC-T cell interaction following gp96 immunization and in general.