High levels of antibodies to the CD4 binding domain of human immunodeficiency virus type 1 glycoprotein 120 are associated with faster disease progression

Human monoclonal antibodies (Abs) to the CD4 binding domain of human immunodeficiency virus (HIV) type 1 glycoprotein (gp) 120 (gp120(CD4bd)) inhibit gp120 presentation to gp120-specific T helper (Th) cells. Since Th responses are critical to control HIV, anti-gp120(CD4bd) Abs could be involved in HIV pathogenesis. Therefore, anti-gp120(CD4bd) Ab levels were compared in serum samples from matched pairs of HIV-positive rapid progressors (RPs) and slow progressors (SPs). Many RPs had higher levels of anti-gp120(CD4bd) Abs than their corresponding SPs. However, Ab levels to whole gp120 and to its C5 domain were similar. Hence, the higher levels of anti-gp120(CD4bd) Abs detected in the serum of RPs do not reflect generalized increases in Ab levels to whole gp120. Moreover, anti-gp120(CD4bd) Ab levels correlated with the amount of inhibition of gp120-specific Th proliferation in the presence of respective serum immunoglobulin G. These findings document a novel mechanism of HIV pathogenesis mediated by anti-gp120(CD4bd) Abs exhibiting suppressive activity on gp120 presentation.