The capacity to induce cross-presentation dictates the success of a TLR7 agonist-conjugate vaccine for eliciting cellular immunity.
Covalent conjugation of TLR agonists to protein Ags often facilitates the generation of a CD8(+) T cell response. However, mechanisms underlying the efficacy of the conjugate over its unconjugated counterpart have been largely uninvestigated. In this study, we show that conjugation of a TLR7 agonist enhances CD8(+) T cell responses without affecting Ag persistence and with minimal impact on cellular uptake of the Ag in vivo. Instead, the conjugated form induced a robust accumulation of dendritic cells (DCs) in regional lymph nodes. Perhaps more importantly, cross-presentation in DCs was detected only when the Ag was delivered in the conjugated form with the TLR7 agonist. Collectively, these data represent the first demonstration that a TLR agonist-Ag conjugate elicits CD8(+) T cell responses based not on its capacity to induce DC maturation or Ag persistence and uptake, but on the engagement of DC cross-presentation pathways.
Oh
Jason Z
JZ
Integrated Department of Immunology, University of Colorado, Denver, CO 80206, USA.
Kedl
Ross M
RM
D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D018074:Vaccines, Conjugate / Q000276:immunology*
D000941:Antigens; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D018074:Vaccines, Conjugate; D010047:Ovalbumin