Development of dectin-1-binding peptides targeting dendritic cells for antigen delivery via ribosome display

Dendritic cells (DCs) are professional antigen-presenting cells that play a central role in initiating and shaping adaptive immune responses. Targeting antigens to DCs has emerged as a promising strategy to enhance vaccine efficacy and tailor desired immune responses. While antibodies are well established as targeting molecules for DCs, the use of peptides remains underexplored despite their favorable tissue penetration and their ability to offer design flexibility. Here, we report the identification of dectin-1-binding peptides using a ribosome display-based in vitro directed evolution system. Dectin-1 is a C-type lectin receptor expressed on murine CD11b⁺ and human CD1c⁺ DCs, which plays a key role in antigen uptake and in directing immune responses toward specific pathways, particularly the Th17 pathway. Using recombinant murine dectin-1 as bait, we performed four rounds of ribosome display selection and obtained peptides with high affinity. Selected peptides fused to enhanced green fluorescent protein showed binding to recombinant dectin-1 and native dectin-1-expressing cells, including bone marrow-derived DCs. These results demonstrated the feasibility of peptide-based molecular targeting toward dectin-1⁺ DCs, which would not only provide a versatile platform for the development of next-generation vaccines and immunotherapies, but also a valuable tool for dissecting the functional roles of dectin-1⁺ DCs in immune regulation.