Viral infection polarizes monocyte-derived dendritic cells (moDC) to initiate type 1 immunity, providing a blueprint for differentiating moDC into inducers of type 1 immune responses that may be effective against tumors. During infection, viruses infect both moDCs and the surrounding tissue, an environment that generates a rich pool of intracellular and extracellular MHC class I and II epitopes, the amino acid sequences of which share substantial sequence overlap (i.e. homologous). Previous work has shown that these homologous MHC epitopes serve as a type of pathogen associated molecular pattern (PAMP), that itself drives moDC type 1 polarization. However, the mechanism(s) through which homologous MHC epitopes reprogram moDCs into a more potent, type 1 polarizing state remain poorly defined. Utilizing single cell RNA sequencing (scRNA-seq), we found that mouse BMDCs loaded with homologous LCMV MHC peptide epitopes upregulated the development of a terminally differentiated cDC1-like cluster characterized by high expression of Batf3, Irf8, Zeb1, Zfp366 and Ly75, and high enrichment in antiviral response pathways. Transcriptomic and proteomic profiling of both mouse BMDC and human moDC linked the induction of the cDC1-like phenotype to mTORC1 inhibition which drives NF-kB-mediated IL-12 gene expression. Inhibition of mTOR enhanced the cDC1-like phenotype as well as DC-mediated cytotoxic T-cell responses. Importantly, the cDC1-like gene signature characterized in mouse BMDC was also upregulated in human clinical moDC vaccine products generated through a methodology that enforces homologous class I and II antigenic loading, demonstrating an evolutionarily conserved phenotype with clinical/translational potential. This work reframes antigen as an active determinant of DC fate, rather than merely passive cargo. By enhancing the cDC1-like phenotype in moDCs, this mechanism can be leveraged for moDC therapies against diseases like cancer in which development of type 1 immune responses are critical to successful outcomes.