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Multiple effector functions mediated by human immunodeficiency virus-specific CD4(+) T-cell clones.

P J Norris·M Sumaroka·C Brander·H F Moffett·S L Boswell·T Nguyen·Y Sykulev·B D Walker·E S Rosenberg
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Abstract

Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-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 Gag 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 Gag. Peptide recognition by all clones examined induced cell proliferation, gamma interferon (IFN-gamma) 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, serine esterase 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 Gag protein and suggest that cytolytic activity may be a component of the antiviral effect of these cells.

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Amino Acid SequenceAnti-Bacterial AgentsAntibodiesBrefeldin ACD4-Positive T-LymphocytesClone CellsCyclophilinsCytotoxicity, ImmunologicDose-Response Relationship, DrugEgtazic AcidEpitopesHIV Core Protein p24HIV InfectionsHIV-1HumansInterferon-gammaMacrolidesMaleMiddle AgedMolecular Sequence DataProtein BindingT-Lymphocytes, Helper-Inducerfas ReceptorComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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P J Norris, M Sumaroka, C Brander, H F Moffett, S L Boswell, T Nguyen, Y Sykulev, B D Walker, E S Rosenberg. 2001. Multiple effector functions mediated by human immunodeficiency virus-specific CD4(+) T-cell clones.. https://doi.org/10.1128/jvi.75.20.9771-9779.2001

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