This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hioe, C. E. Articles by Zolla-Pazner, S. Search for Related Content PubMed PubMed Citation Articles by Hioe, C. E. Articles by Zolla-Pazner, S. Pubmed/NCBI databases Substance via MeSH

 Previous Article  |  Next Article 

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.

---

^* 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.

---

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.

This article has been cited by other articles:

• Bouhlal, H., Chomont, N., Requena, M., Nasreddine, N., Saidi, H., Legoff, J., Kazatchkine, M. D., Belec, L., Hocini, H. (2007). Opsonization of HIV with Complement Enhances Infection of Dendritic Cells and Viral Transfer to CD4 T Cells in a CR3 and DC-SIGN-Dependent Manner. J. Immunol. 178: 1086-1095 [Abstract] [Full Text]  
• Okazaki, T., Pendleton, C. D., Sarobe, P., Thomas, E. K., Iyengar, S., Harro, C., Schwartz, D., Berzofsky, J. A. (2006). Epitope Enhancement of a CD4 HIV Epitope toward the Development of the Next Generation HIV Vaccine. J. Immunol. 176: 3753-3759 [Abstract] [Full Text]  
• Chien, P. C. Jr., Cohen, S., Tuen, M., Arthos, J., Chen, P.-d., Patel, S., Hioe, C. E. (2004). Human Immunodeficiency Virus Type 1 Evades T-Helper Responses by Exploiting Antibodies That Suppress Antigen Processing. J. Virol. 78: 7645-7652 [Abstract] [Full Text]  
• Kaufmann, D. E., Bailey, P. M., Sidney, J., Wagner, B., Norris, P. J., Johnston, M. N., Cosimi, L. A., Addo, M. M., Lichterfeld, M., Altfeld, M., Frahm, N., Brander, C., Sette, A., Walker, B. D., Rosenberg, E. S. (2004). Comprehensive Analysis of Human Immunodeficiency Virus Type 1-Specific CD4 Responses Reveals Marked Immunodominance of gag and nef and the Presence of Broadly Recognized Peptides. J. Virol. 78: 4463-4477 [Abstract] [Full Text]  
• Giannecchini, S., Isola, P., Sichi, O., Matteucci, D., Pistello, M., Zaccaro, L., Del Mauro, D., Bendinelli, M. (2002). AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Failure To Protect and Possible Enhancement of Challenge Infection by Four Cell-Based Vaccines Prepared with Autologous Lymphoblasts. J. Virol. 76: 6882-6892 [Abstract] [Full Text]