Immunological characteristics of the putative CD4-binding site of the HIV-1 envelope protein

As an extension of previous studies demonstrating the immunosuppressive properties of gp120, we have analyzed the immunological characteristics of gp120 peptides, derived principally from its putative CD4-binding site. Our studies indicate that peptides derived from this region do not stimulate proliferation of lymphocytes from HIV-seropositive donors with relatively normal numbers of CD4+ lymphocytes. No significant proliferation was observed in response to various concentrations of peptide, even in the presence of interleukin-2 (IL-2). Significant proliferation of these lymphocytes was observed in response to two recall antigens, cytomegalovirus (CMV) and tetanus toxoid (TT), and these responses were augmented by IL-2. Peripheral blood mononuclear cells from HIV-seronegative donors were cultured in the presence of TT and CMV and the peptides derived from gp120. Proliferation in the presence of these recall antigens was inhibited by these peptides in a dose-dependent manner. These studies demonstrate that at high concentrations, peptides from the putative CD4-binding site can inhibit proliferation of lymphocytes from normal donors in response to a recall antigen. The apparent immunosuppressive properties of this region highlight the pathogenic role played by HIV-1 envelope protein interactions with host cells.