التفاصيل البيبلوغرافية
| العنوان: |
HLA-DR-Restricted Peptides Identified in The Nef Protein Can Induce HIV Type 1-Specific IL-2IFN-γ-Secreting CD4And CD4CD8T Cells in Humans after Lipopeptide Vaccination. |
| المؤلفون: |
Hanne Gahery, Suzanne Figueiredo, Catherine Texier, Sandra Pouvelle-Moratille, Lucie Ourth, Céline Igea, Mathieu Surenaud, Jean-Gérard Guillet, Bernard Maillere |
| المصدر: |
AIDS Research & Human Retroviruses; Mar2007, Vol. 23 Issue 3, p427-437, 11p |
| مستخلص: |
We screened the Neflaiprotein to identify new HLA-DR-restricted epitopes, because this small protein is expressed early during infection, and specific CD4T 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 CD4T 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-γELISPOT and flow cytometer assays to investigate the capacity of these potential CD4T 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 CD4and CD4CD8T cells secreting IL-2INF-γor IL-2 alone. To conclude, these 26 Nef HLA-DR-restricted peptides could be helpful to better evaluate CD4deficiencies in HIV infection and, for new vaccine designs. [ABSTRACT FROM AUTHOR] |
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