Th1 immune response against HIV-1 Gag p24-derived peptides in mice expressing HLA-A02.01 and HLA-DR1

Using HLA-DR1-transgenic H-2 class II knockout mice, we identified two new HLA-DR1-restricted HIV-1 Gag p24-derived epitopes (Gag₃₂₁₋₃₄₀ and Gag₃₃₁₋₃₅₀) and confirmed the immunogenicity of seven that have been previously described. The human relevance was confirmed for the two new ones (Gag₃₂₁₋₃₄₀ and Gag₃₃₁₋₃₅₀) assaying peripheral blood mononuclear cells from HLA-DR1⁺ HIV-1-infected long-term asymptomatic subjects and showing that Gag₃₃₁₋₃₅₀ could prime CD4⁺ T cells from two HLA-DR1⁺ HIV-1 seronegative donors in vitro. Seven of these epitopes, structurally conserved among HIV-1 clade B isolates, were selected for a comparative evaluation of their Th1 helper potential by immunizing HLA-A02.01/HLA-DR1-transgenic, H-2 class I/class II knockout mice with recombinant mouse invariant chain constructs in which each helper epitope was inserted in association with two reporter HIV-1-derived HLA-A02.01-restricted CD8⁺ T cell epitopes. A T helper effect was demonstrated in all cases, and was particularly strong with epitopes Gag₃₀₁₋₃₂₀, Gag₃₂₁₋₃₄₀ and Gag₂₇₁₋₂₉₀, which should, therefore, be considered in the design of new vaccines.