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Journal of Virology, April 2004, p. 3792-3796, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3792-3796.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Generation and Characterization of Neutralizing Human Monoclonal Antibodies against Human Immunodeficiency Virus Type 1 Tat Antigen

Emmanuel Moreau,1 Johan Hoebeke,2 Daniel Zagury,3 Sylviane Muller,2 and Claude Desgranges1*

INSERM EMI 0334, Hôpital St-Louis, F-75010 Paris,1 UPR 9021 CNRS, Institut de Biologie Moléculaire et Cellulaire, F-67000 Strasbourg,2 Université Pierre et Marie Curie, F-75006 Paris, France3

Received 23 October 2003/ Accepted 24 November 2003

The human immunodeficiency virus Tat regulatory protein is essential for virus replication and pathogenesis. From human peripheral blood mononuclear cells of three Tat toxoid-immunized volunteers, we isolated five Tat-specific human monoclonal antibodies (HMAbs): two full-length immunoglobulin G (IgG) antibodies and three single-chain fragment-variable (scFv) antibodies. The two IgGs were mapped to distinct epitopes within the basic region of Tat, and the three scFvs were mapped to the N-terminal domain of Tat. The three scFvs were highly reactive with recombinant Tat in Western blotting or immunoprecipitation, but results were in contrast to those for the two IgGs, which are sensitive to a particular folding of the protein. In transactivation assays, scFvs were able to inhibit both active recombinant Tat and native Tat secreted by a transfected CEM cell line while IgGs neutralized only native Tat. These HMAbs were able to reduce viral p24 production in human immunodeficiency virus type 1 strain IIIB chronically infected cell lines in a dose-dependent manner.

* Corresponding author. Mailing address: INSERM EMI 0334, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France. Phone: 33 1 42 49 92 69. Fax: 33 1 42 49 48 38. E-mail: claude.desgranges{at}chu-stlouis.fr.

Journal of Virology, April 2004, p. 3792-3796, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3792-3796.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Moreau, E., Belliard, G., Partidos, C. D., Pradezinsky, F., Le Buanec, H., Muller, S., Desgranges, C. (2004). Important B-cell epitopes for neutralization of human immunodeficiency virus type 1 Tat in serum samples of humans and different animal species immunized with Tat protein or peptides. J. Gen. Virol. 85: 2893-2901 [Abstract] [Full Text]  


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