The presence of T cell epitopes is important for induction of antibody responses against antigens directed to DEC205+ dendritic cells

Abstract

In vivo antigen targeting to dendritic cells (DCs) has been used as a way to improve immune responses. Targeting is accomplished with the use of monoclonal antibodies (mAbs) to receptors present on the DC surface fused with the antigen of interest. An anti-DEC205 mAb has been successfully used to target antigens to the DEC205⁺CD8α⁺ DC subset. The administration of low doses of the hybrid mAb together with DC maturation stimuli is able to activate specific T cells and induce production of high antibody titres for a number of different antigens. However, it is still not known if this approach would work with any fused protein. Here we genetically fused the αDEC205 mAb with two fragments (42-kDa and 19-kDa) derived from the ~200 kDa Plasmodium vivax merozoite surface protein 1 (MSP1), known as MSP1₄₂ and MSP1₁₉, respectively. The administration of two doses of αDEC-MSP1₄₂, but not of αDEC-MSP1₁₉ mAb, together with an adjuvant to two mouse strains induced high anti-MSP1₁₉ antibody titres that were dependent on CD4⁺ T cells elicited by peptides present in the MSP1₃₃ sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205⁺ DCs increases antibody responses.