Ribosome display-derived CD207-binding peptides enhance humoral responses via Langerhans cell-targeted antigen delivery

Langerhans cells (LCs) are specialized antigen-presenting cells residing in the epidermis. LCs express the C-type lectin receptor CD207, which mediates antigen uptake and internalization. Because epidermal LCs encounter antigens at the skin surface and regulate subsequent immune responses, CD207 provides a rational molecular target for skin-based antigen delivery strategies. In this study, we performed ribosome display using a structurally constrained cyclic peptide library to identify mCD207-binding peptides. After three rounds of bio-panning, three candidate peptide-EGFP fusion constructs exhibited micromolar affinity for recombinant mCD207, with the strongest binder showing a KD of approximately 0.3 μM. Peptide 2 and peptide 3 selectively bound to mCD207-expressing mammalian cells and primary mouse LCs. Fusion of peptide 3 to a model antigen enhanced antigen delivery to LCs and increased antigen-specific serum IgG levels following intradermal immunization in mice. These findings identify ribosome display-derived mCD207-targeting peptides as novel molecular tools for selective antigen delivery to epidermal LCs.