Design of a polyepitope construct for the induction of HLA‐A0201‐restricted HIV 1‐specific CTL responses using HLA‐A0201 transgenic, H‐2 class I KO mice

HLA‐A*0201 transgenic, H‐2Db/mouse β2‐microglobulin double‐knockout mice were used to compare and optimize the immunogenic potential of 17HIV 1‐derived,HLA‐A0201‐restricted epitopic peptides. A tyrosine substitution in position 1 of the epitopic peptides, which increases both their affinity for and their HLA‐A0201 molecule stabilizing capacity, was introduced in a significant proportion, having verified that such modifications enhance their immunogenicity in respect of their natural antigenicity. Based on these results, a 13‐polyepitope construct was inserted in the pre‐S2 segment of the hepatitis B middle glycoprotein and used for DNA immunization. Long‐lasting CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal with cross‐recognition in several cases of their most common natural variants.