Screening for simulation peptide specifically binding to the first and the second extra-cellular domain of CCR5 and its therapeutic effect on mice with autoimmune encephalomyelitis / 第二军医大学学报

ABSTRACT

Objective:To screen for simulation peptide binding specifically to the first and the second extra-cellular domain of CC chemokine receptor 5(CCR5),and to observe their therapeutic effect on mice with experimental autoimmune encephalomyelitis(EAE).Methods:Phage display peptide library was used to screen for peptide sequence binding specifically to CCR5;ELISA was used to identify its binding activity and analyze its DNA sequence.The simulation peptide was synthesized and was injected into abdominal cavity of the EAE mice.Spinal cord tissues were obtained and the pathologic changes were studied by H-E staining in EAE control group and simulation peptide group.Results:Twenty phage clones were randomly chosen for identification and ELISA showed that there were eighteen clones had a strong binding activity with CCR5.The positive clones were sequenced and four peptides of high frequency were obtainedSTFTTTL,TPIPQLL,SLPLPKP,and QTSSAAL.Mean clinical score of mice in the EAE model group was 3 and that of the simulation peptide group was 1.H-E staining found that the spinal cord tissues in EAE model group had great number of inflammatory cells and evident demyelination changes;the simulation peptide group had less inflammatory cells and no demyelination changes.The four short peptides had an effect of suppressing and delaying the development of EAE,with the average inhibition rate being 43%(P