HLA-DR-restricted peptides identified in the Nef protein can induce HIV type 1-specific IL-2/IFN-gamma-secreting CD4+ and CD4+ /CD8+ T cells in humans after lipopeptide vaccination. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue AIDS Research and Human Retroviruses Année : 2007

HLA-DR-restricted peptides identified in the Nef protein can induce HIV type 1-specific IL-2/IFN-gamma-secreting CD4+ and CD4+ /CD8+ T cells in humans after lipopeptide vaccination.

Résumé

We screened the Neflaiprotein to identify new HLA-DR-restricted epitopes, because this small protein is expressed early during infection, and specific CD4(+) T cells are critical for effective immunity in HIV-1 infection. We synthesized a set of peptides that covers the sequence of the Nef protein, and performed binding assays using 10 common HLA-DR molecules. We defined four large regions in this protein able to bind very efficiently to eight HLADR molecules. We took advantage of healthy volunteers immunized with an HIV-1 lipopeptide vaccine that contains three of the four HLA DR-restricted regions to investigate their capacities to stimulate T cells. In 11 vaccinated volunteers, typed for their class II molecules, we were able to correlate sequences of the vaccine displaying binding activities to specific HLA-DR molecules and the induction of CD4(+) T cell proliferation. To identify potential HLA-DR epitopes, we synthesized 31 15-mer peptides and showed that 26 bound to one or more HLA-DR molecules. Interestingly, 12 of the 26 15-mer peptides identified are included in the sequence of lipopeptides. We used IFN-gamma ELISPOT and flow cytometer assays to investigate the capacity of these potential CD4(+) T cell epitopes to induce specific T cell responses. We showed that seven of these peptides were able to stimulate HIV-specific T cell responses in five of six tested volunteers. These cells are Nef-specific CD4(+) and CD4(+) CD8(+) T cells secreting IL-2/INF-gamma or IL-2 alone. To conclude, these 26 Nef HLA-DR-restricted peptides could be helpful to better evaluate CD4(+) deficiencies in HIV infection and, for new vaccine designs.
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Dates et versions

hal-00529938 , version 1 (27-10-2010)

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Citer

Hanne Gahery, Suzanne Figueiredo, Catherine Texier, Sandra Pouvelle-Moratille, Lucie Ourth, et al.. HLA-DR-restricted peptides identified in the Nef protein can induce HIV type 1-specific IL-2/IFN-gamma-secreting CD4+ and CD4+ /CD8+ T cells in humans after lipopeptide vaccination.. AIDS Research and Human Retroviruses, 2007, 23 (3), pp.427-37. ⟨10.1089/aid.2006.0075⟩. ⟨hal-00529938⟩

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