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135 Presentation of HIV gp120 Antigen to CD4 T-Helper Cells Is Prevented by Antibodies
P. Chien, Jr.1, M. Tuen1, P. D. Chen1, S. Cohen1, C. Kleeberger2, J. Giorgi3, J. Phair4, S. Zolla-Pazner1, and C. E. Hioe*1
1New York Univ. and VA Med Ctrs, NY, USA; 2Johns Hopkins Sch. of Publ. Hlth., Baltimore, MD, USA; 3UCLA Med. Sch., Los Angeles, CA, USA; and 4Northwestern Med. Sch., Chicago, IL, USA
Background: HIV-specific CD4 T-cell responses, particularly to gp120, are weak or absent in most HIV-infected patients. Although the dearth of these responses can be attributed to the destruction of env-specific cells by the virus, other factors also contribute to the suppression of these virus-specific responses. Our work has shown that human monoclonal antibodies (mAbs) specific for the CD4 binding domain of gp120 (gp120CD4BD), when complexed with gp120, “hijack” the antigen preventing its processing necessary for the presentation to gp120-specific CD4 T cells. MAbs to other gp120 epitopes do not exhibit this activity. Gp120-specific T-cell responses are also inhibited in the presence of serum Abs from HIV-infected individuals, and the levels of inhibition correlate with the titers of anti-gp120CD4BD Abs present in the serum. These results suggest that the generation of high levels of these Abs during HIV infection may suppress anti-viral CD4 T-cell responses in vivo as they do in vitro and could exacerbate disease progression in the infected hosts.
Methods: To examine the role of anti-gp120CD4BD Abs in HIV disease progression, we compared the titers of anti-gp120CD4BD Abs in the sera of 14 matched pairs of HIV+ rapid progressors and HIV+ slow/nonprogressors from the Multicenter AIDS Cohort Study.
Results: Prior to AIDS, levels of anti-gp120CD4BD Abs were higher in the sera of HIV+ rapid progressors than in slow/nonprogressors; Ab titers to the whole gp120 and to the C5 domain of gp120 were not significantly different in these groups.
Conclusions: Taken together, our study suggests that anti-gp120CD4BD Abs have suppressive effects on anti-viral CD4 T-cell responses and that the presence of high levels of these Abs during infection may contribute to disease progression. Hence, induction of such Abs by vaccines may not be beneficial. Indeed these Abs could be detrimental to the immune responses that these vaccines are designed to elicit.
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