Targeting antigen to CD40 reinforces dendritic cells to cross-prime antigen-specific CD8+ T cells (APP3P.110)

Abstract

Abstract Dendritic cells are major antigen-presenting cells that can efficiently cross-prime antigen-specific CD8+ T cells. Thus, targeting antigen to dendritic cells via surface receptors is an appealing strategy to mount CD8+ T cell-mediated immunity against intracellular pathogens and cancers. Nonetheless, which targeted receptor is the most efficient at priming CD8+ T cells remains elusive. Herein, we report the superior function of CD40 over nine different lectins and scavenger receptors at priming antigen-specific CD8+ T cells. A quantitative analysis of intracellular trafficking of antibody-bound receptors revealed that αCD40 monoclonal antibody localized mainly at the plasma membrane and subsequently accumulated at early endocytic compartments whereas αLOX-1 and αDectin-1 monoclonal antibodies localized at both early and late endocytic compartments in dendritic cells. Regardless of the differences in their subcellular localizations, targeting antigen to CD40 and lectins resulted in the same pattern of peptide epitope-specific IFNg+CD8+ T cell responses. We also report that poly(I:C) can significantly enhance both CD8+ and CD4+ T cell responses elicited by targeting antigen to CD40 in both human in vitro and in human CD40 transgenic mouse in vivo settings. This study provides key information for the rational design of DC-targeting vaccines against cancers and intracellular pathogens.