DESIGN OF A POLYEPITOPIC CONSTRUCT FOR THE INDUCTION OF HLA-A2.1 RESTRICTED HIV 1 SPECIFIC CTL RESPONSES USING HHD MICE

摘要

H-2 class I negative, HLA-A2.1 transgenic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumour-associated CTL epitopes and HIV 1-derived epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. A tyrosine substitution in position 1 of the HIV 1-derived epitopic peptides, which increases both their affinity for and their HLA-A2.1 molecule stabilizing capacity, was introduced in a significant proportion of them. DNA immunizations were performed using a construct comprising nucleic acids encoding the epitopes inserted into the pre-S2 segment of the hepatitis B middle glycoprotein. CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal.