Portal de Periódicos da CAPES

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

2007; Wiley; Volume: 37; Issue: 9 Linguagem: Inglês

10.1002/eji.200636819

1521-4141

Anthony Pajot, Aurélie Schnuriger, Arnaud Moris, Audrey Rodallec, David M. Ojcius, Brigitte Autran, François A. Lemonnier, Yu Chun Lone,

Immunotherapy and Immune Responses

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 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 Gag(301-320),Gag(321-340 )and Gag(271-290), which should, therefore, be considered in the design of new vaccines.