Helper and cytotoxic T cell responses of HIV type 1-infected individuals to synthetic peptides of HIV type 1 Rev.

In cell-mediated immunity T cells recognize peptide fragments of the antigenic protein in association with major histocompatibility complex (MHC) proteins. Synthetic 9- to 16-mer peptides have been widely used to identify the region(s) of a protein that act as T cell epitope. Here, we report antigenic peptides identified on HIV-1 regulatory protein Rev. Four synthetic peptides (amino acids 9-23, 25-39, 33-48, and 41-56) were first shown to stimulate T helper (Th) cell proliferation in peripheral blood lymphocytes (PBLs) derived from HIV-seropositive (HIV+) individuals. The same peptides induced cytotoxic T lymphocyte (CTL) activities toward the autologous target cells incubated with the peptides. Both responses were specific to the HIV infection as HIV-seronegative (HIV-) control individuals showed no significant proliferative or cytotoxic activity. The proliferating cells were CD4+ T cells, and CTL activity was mediated by CD8+ human leukocyte antigen (HLA)-restricted T cells. The identification of peptides containing epitopes that can induce both Th and CTL responses to regulatory proteins of HIV-1 in infected individuals might be important for vaccine development against AIDS. Since early regulatory proteins of HIV are expressed by the infected cells before the initiation of the synthesis of structural proteins, a CTL response against these proteins could destroy the infected cells before the release of infectious virions.