Covalent conjugation of TLR7 agonists to protein antigens is an effective vaccine formulation that enhances the immunogenicity of the antigen and elicits adaptive immune responses. Other studies have shown a similar enhancement of adaptive immune responses when using antigens conjugated to agonists targeting TLR2, TLR4 or TLR9. However, the mechanisms underlying the efficacy of conjugation remain poorly defined. Mechanisms by which other types of vaccine adjuvants enhance the immunogenicity of antigens have been examined for several decades. These studies implicated changes in stability of the antigen due to the immunostimulatory activities of the adjuvant. Therefore, I hypothesized that conjugation of TLR7 agonist to a protein antigen alters properties of the antigen in a manner that contributes to an overall enhancement in immunogenicity of the conjugated product. Through my studies, I found that conjugation influences the immunogenicity of the antigen by first facilitating the efficient recruitment of DCs into the lymph node and the induction of efficient cross-presentation by the antigen-bearing DCs. In this thesis, I also describe divergent effects of two crucial cytokines, Type I IFN and 1L-12, induced by the TLR7 agonist-antigen conjugate in leading to efficient cross-priming. I demonstrate that TLR7-driven CD8⁺ T cell responses require not one, but both Type I IFN and IL-12. I show a crucial role for Type I IFN in recruitment and accumulation of activated Langerhans cells and CDα8⁺ DC subsets into the lymph node and initiation of cross-presentation mediated by these cells. Collectively, these studies demonstrate that efficient cross-priming can be mediated by multiple DC subsets and reveal new pathways involved in cross-presentation that may further our understanding of vaccine designs.