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Journal of Virology, November 2001, p. 10950-10957, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10950-10957.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Inhibition of Human Immunodeficiency Virus Type 1 gp120 Presentation to CD4 T Cells by Antibodies Specific for the CD4 Binding Domain of gp120

Catarina E. Hioe,^1,* Michael Tuen,¹ Peter C. Chien Jr.,¹ Gareth Jones,² Silvia Ratto-Kim,³ Philip J. Norris,⁴ Walter J. Moretto,⁵ Douglas F. Nixon,⁵ Miroslaw K. Gorny,¹ and Susan Zolla-Pazner¹

New York VA Medical Center and New York University School of Medicine, New York, New York 10010¹; Department of Immunology, Chelsea and Westminster Hospital, London SW10 0NH, United Kingdom²; Henry M. Jackson Foundation and Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850³; Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114⁴; and Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141⁵

Received 13 March 2001/Accepted 16 August 2001

Human immunodeficiency virus (HIV)-specific CD4 T-cell responses, particularly to the envelope glycoproteins of the virus, are weak or absent in most HIV-infected patients. Although these poor responses can be attributed simply to the destruction of the specific CD4 T cells by the virus, other factors also appear to contribute to the suppression of these virus-specific responses. We previously showed that human monoclonal antibodies (MAbs) specific for the CD4 binding domain of gp120 (gp120_CD4BD), when complexed with gp120, inhibited the proliferative responses of gp120-specific CD4 T-cells. MAbs to other gp120 epitopes did not exhibit this activity. The present study investigated the inhibitory mechanisms of the anti-gp120_CD4BD MAbs. The anti-gp120_CD4BD MAbs complexed with gp120 suppressed gamma interferon production as well as proliferation of gp120-specific CD4 T cells. Notably, the T-cell responses to gp120 were inhibited only when the MAbs were added to antigen-presenting cells (APCs) during antigen pulse; the addition of the MAbs after pulsing caused no inhibition. However, the anti-gp120_CD4BD MAbs by themselves, or as MAb/gp120 complexes, did not affect the presentation of gp120-derived peptides by the APCs to T cells. These MAb/gp120 complexes also did not inhibit the ability of APCs to process and present unrelated antigens. To test whether the suppressive effect of anti-gp120_CD4BD antibodies is caused by the antibodies' ability to block gp120-CD4 interaction, APCs were treated during antigen pulse with anti-CD4 MAbs. These treated APCs remained capable of presenting gp120 to the T cells. These results suggest that anti-gp120_CD4BD Abs inhibit gp120 presentation by altering the uptake and/or processing of gp120 by the APCs but their inhibitory activity is not due to blocking of gp120 attachment to CD4 on the surface of APCs.

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^* Corresponding author. Mailing address: VA Medical Center, 423 E. 23rd St., Room 18-124 North, New York, NY 10010. Phone: (212) 263-6769. Fax: (212) 951-6321. E-mail: hioec01{at}med.nyu.edu.

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Journal of Virology, November 2001, p. 10950-10957, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10950-10957.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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