The Th1 immune response against HIV-1 Gag p24-derived peptides in mice expressing HLA-A02.1 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 (Gag_321-340 and Gag_331-350) and confirmed the immunogenicity of seven that have been previously described. The human relevance was confirmed for the two new ones (Gag_321-340 and Gag_331-350) assaying peripheral blood mononuclear cells from HLA-DR1⁺ HIV-1-infected long-term asymptomatic subjects and showing that Gag_331-350 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 Thl 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 Gag_301-320, Gag_321-340 and Gag_271-290, which should, therefore, be considered in the design of new vaccines.