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213 Identification of a Promiscuous HLA-DQ HIV Nef Peptide That Induces IFN-gamma Producing Memory CD4+ T Cells
V. Pancré*1, B. Georges1, G. Angyalosi1, F. Castelli2, B. Maillère2, A. Bouzidi3, and C. Auriault1
1 IBL, Lille, France; 2 CEA, Gif sur Yvette, France; and 3Sedac Therapeutics, Lille, France
We described the highly conserved sequence 56-68 of the HIV Nef protein as the first promiscuous HLA-DQ HIV derived peptide. Nef peptide exhibits an albeit rare capacity to bind 6 different HLA-DQ molecules, whereas no binding is observed on the 10 HLA-DR molecules tested. In agreement with these data, after immunization with Nef peptide, HLA-DQ transgenic Abeta° mice display a vigorous cellular and humoral response, whereas the specific immune response of HLA-DR expressing mice is minimal. The promiscuous potentiality of Nef 56-68 peptide in human has been confirmed by ex vivo immunization experiments of CD4+ T cells from 14 healthy donors expressing different HLA genotypes. Nef 56-68-specific CD4+ T cells acquire rapidly a phenotype of memory cells and are characterized by the preferential usage of Vbeta6.1 gene segment and a predominant production of IFN-gamma. So, Nef 56-68 peptide represents an interesting candidate for vaccinal strategy and/or cellular immunotherapy in HIV-infected patients.
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