Human immunodeficiency virus type 1 Nef epitopes recognized in HLA-A2 transgenic mice in response to DNA and peptide immunization

We investigated the immune response against a human immunodeficiency Virus type I (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the human major histocompatibility complex (MHC) class I molecule HLA- A201. Ten potential HLA-AP binding 9-mer Nef peptides were identified by a computer-based search algorithm. By a cell surface MHC class I stabilizatio n assay, four peptides were scored as good binders, whereas two peptides bo und weakly to HLA-AP. After DNA immunization. cytotoxic T lymphocyte (CTL) responses were predominantly directed against the Nef 44-52, 81-89, and 85- 93 peptides. Interestingly. the 44-52 epitope resides outside the regions o f Nef where previously described CTL epitopes are clustered. Dominance amon g Nef-derived peptides did not strictly correlate with HLA-A2 binding, in t hat only one of the high-affinity binding peptides was targeted in the CTL response. The 44-52, 85-93, and 139-147 peptides also generated specific CT Ls in response to peptide immunization. T helper cell proliferation was det ected after stimulation with 20-mer peptides in vitro. Three Nef regions (1 6-35, 106-125, and 166-185) dominated the T helper cell proliferation. The implications of these results for the development of DNA-based vaccines aga inst HIV is discussed. (C) 2000 Academic Press.