The interactions of peptides with the innate immune system studied with use of T7 phage peptide display

The icosahedral T7 phage (diameter similar to 65 nm) displaying random pept ides at the carboxy-terminus of the phage coat proteins was used as a model for drug and gene delivery vehicles containing peptide ligands. We found t hat displayed peptides were recognized by natural antibodies and induced co mplement activation. Strikingly, the phage inactivation by complement was p eptide-specific that implied the existence of numerous natural antibodies w ith different peptide specificity. Selection of phage that avoided inactiva tion by complement allowed the identification of peptides that protected th e phage by binding to serum proteins. In rat blood, peptides with carboxy-t erminal lysine or arginine residues protected the phage against complement- mediated inactivation by binding C-reactive protein. In human serum, a numb er of protective peptides with tyrosine residues were selected. The recogni tion of displayed peptides by natural antibodies appears to represent a uni versal mechanism for activation of complement at sites that contain identic al or homologous proteins with exposed carboxy-termini.