Novel promiscuous HLA‐DQ HIV Nef peptide that induces IFN‐ γ ‐producing memory CD4 + T cells

SUMMARY We describe the highly conserved sequence 56–68 of the HIV Nef protein as the first promiscuous HLA‐DQ HIV‐derived peptide. The Nef peptide exhibits an albeit rare capacity to bind 6 different HLA‐DQ molecules whereas no binding is observed with the 10 HLA‐DR molecules tested. In agreement with these data, after immunization with the Nef peptide, HLA‐DQ transgenic Aβ° mice display a vigorous cellular and humoral response while the specific immune response of HLA‐DR expressing mice is minimal. The promiscuous potentiality of the Nef 56–68 peptide in humans has been confirmed by ex vivo immunization experiments with CD4 + T cells from 14 healthy donors expressing different HLA genotypes. Nef 56–68 specific CD4 + T cells rapidly acquire a memory cell phenotype and are characterized by the preferential usage of the TCR Vβ 6·1 gene segment and predominant production of IFN‐γ. Taken together, these data indicate that the Nef 56–68 peptide constitutes an attractive component of vaccines aiming at inducing or enhancing HIV‐specific T cell immunity.