
<ArticleTitle>Multiple effector functions mediated by human immunodeficiency virus-specific CD4(+) T-cell clones.</ArticleTitle>
<AbstractText>Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) <prot>Gag</prot>-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain to be defined. In this study, we generated CD4(+) T-cell clones specific for <prot>Gag</prot> from HIV-1-infected persons with vigorous Gag-specific responses detectable in peripheral blood mononuclear cells. Multiple peptides containing T helper epitopes were identified, including a minimal peptide, VHAGPIAG (amino acids 218 to 226), in the cyclophilin binding domain of <prot>Gag</prot>. Peptide recognition by all clones examined induced cell proliferation, <prot>gamma interferon</prot> (<prot>IFN-gamma</prot>) secretion, and cytolytic activity. Cytolysis was abrogated by concanamycin A and EGTA but not brefeldin A or anti-Fas antibody, implying a perforin-mediated mechanism of cell lysis. Additionally, <prot>serine esterase</prot> release into the extracellular medium, a marker for cytolytic granules, was demonstrated in an antigen-specific, dose-dependent fashion. These data indicate that T helper cells can target multiple regions of the p24 <prot>Gag</prot> protein and suggest that cytolytic activity may be a component of the antiviral effect of these cells.</AbstractText>
