HLA A2 subtype distribution among Beijing Chinese and its effect on CTL response in vitro to p53 protein based synthetic peptides loaded on dendritic cells
Objective To explore the HLA A2 subtype distribution among Beijing Chinese and its effect on CTL response in vitro to p53 protein based synthetic peptides loaded on dendritic cells. Methods The distribution of HLA A2 genotype and subtypes were analyzed with PCR SSP.The p53 149 157 , p53 264 272 ,and HBVc 18 27 which had high affinity with HLA A201 molecule, were loaded individually on human umbilical cord blood dendritic cells cultured with GM CSF+IL 4 to induce specific CTLs. Results There were 53 cases of HLA A2 genotype among 200 healthy Beijing Chinese , HLA A201 and A207 were the two major subtypes. Dendritic cells (DC), cultured with GM CSF+IL 4, showed enhanced HLA Ⅰ and HLA Ⅱ molecules expression following subsequent addition of TNF α.HLA A201 restricted CTL responses specific to all the studied peptides were readily induced from autologous PBMC by peptide loaded to the DCs. However, HLA A207 restricted CTL response could only be induced by repeatedly using peptide p53 264 272 .Conclusions The distribution profile of HLA A2 subtypes among Beijing Chinese is relatively unique. DC obtained from human cord blood could be used as an effective adjuvant of peptides to overcome the self tolerance to p53 to induce specific CTL responses. Change of one amino acid in the peptide binding region of A2 molecule might significantly influence the antigen presenting ability of certain peptides.