Design of a polyepitope construct for the induction of HLA-A0201-restricted HIV 1-specific CTL responses using HLA-A*0201 transgenic, H-2 class IKO mice

HLA-A*0201 transgenic, H-2D(b)/mouse beta2-microglobulin double-knockout mi ce were used to compare and optimize the immunogenic potential of 17HIV 1-d erived, HLA-A0201-restricted epitopic peptides. A tyrosine substitution in position 1 of the epitopic peptides, which increases both their affinity fo r and their HLA-A0201 molecule stabilizing capacity, was introduced in a si gnificant proportion, having verified that such modifications enhance their immunogenicity in respect of their natural antigenicity. Based on these re sults, a 13-polyepitope construct was inserted in the pre-S2 segment of the hepatitis B middle glycoprotein and used for DNA immunization. Long-lastin g CTL responses against most of the inserted epitopes could be elicited sim ultaneously in a single animal with cross-recognition in several cases of t heir most common natural variants.