SPECIFICITY OF HELPER T-CELLS GENERATED FROM MACAQUES INFECTED WITH ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS

Deletion of the simian immunodeficiency virus (SIV) nef gene leads to an attenuated virus phenotype in vivo. We have previously shown that t hese viruses induce a potent cellular immune response in macaques. To extend these studies, we established virus-specific short-term T-cell lines from four rhesus macaques infected with a nef deletion mutant of SIV, These T-cell lines proliferated upon restimulation with whole SI V or SIV gp140 antigen in vitro. The proliferating cells were characte rized as CD4(+) helper T-cells (TH) and their antigen recognition was MHC class II DR-restricted. After antigenic stimulation, they transcri bed mRNA for various TH1- and TH2-like cytokines, Using these SIV-spec ific cell lines, a variety of helper T-cell epitopes in the SIV Env pr otein were determined with overlapping peptides, TH epitopes were iden tified throughout the whole SIV Env including both constant and variab le regions. Although the recognition of TH epitopes was heterogeneous among different animals, five more broadly reactive T-cell epitopes we re identified. As expected, recognition was associated with the MHC cl ass II DRB background of the animals. This is the first report on help er T-cell epitopes in SIV-infected monkeys. Such studies should be of considerable significance for AIDS/vaccine research.