Design, Optimization and structure-activity relationship study of CD2 derived peptides for immunomodulation

Abstract

CD2 plays important roles of adhesion and co-stimulation in antigen recognition and T cell activation. The aim of this study is to design I?-turn peptides from CD2 ligand binding epitopes to modulate CD2-CD58 interaction for immunomodulation.12-amino acid parent peptides designed from rat CD2 (cER and cVL) and human CD2 (cAQ and cIL) were subjected to truncation and alanine scanning. The inhibitory activity of the peptides was evaluated by E-rosetting as well as a newly developed heterotypic adhesion assay using OVCAR and Jurkat cells. NMR and molecular modeling studies were performed to arrive at the 3D structure of the peptides.The minimum inhibitory sequence (cVR, cQT, cIN) determined by truncation study, adopted stable I?-turn structure. Alanine scanning suggested the important roles of particular residues in hexapeptide cEL. Structure-activity relationship study supported the hypothesis that small cyclic peptides derived from CD2 could modulate CD2-CD58 interaction by mimicking native I?-turn epitopes.