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Journal of Virology, October 2001, p. 9771-9779, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9771-9779.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Multiple Effector Functions Mediated by Human Immunodeficiency Virus-Specific CD4+ T-Cell Clones

Philip J. Norris,1 Marina Sumaroka,2 Christian Brander,1 Howell F. Moffett,1 Steven L. Boswell,3 Tam Nguyen,1 Yuri Sykulev,2 Bruce D. Walker,1 and Eric S. Rosenberg1,*

Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021141; Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 191072; and Fenway Community Health Center, Boston, Massachusetts 021153

Received 13 April 2001/Accepted 6 July 2001

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.

* Corresponding author. Mailing address: Massachusetts General Hospital, GRJ 504, 55 Fruit St., Boston, MA 02114. Phone: (617) 724-7519. Fax: (617) 726-7416. E-mail: erosenberg1{at}partners.org.

Journal of Virology, October 2001, p. 9771-9779, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9771-9779.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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