Blockade of immunoregulatory Fc-signalling by HIV peptides: oligopeptides from HIV gp120 and gp41 bind the Fc portion of IgG and increase the in vitro anti-ssDNA response.

Concomitant ligation of antigen receptors with Fc-receptors negatively signals B cells. Antibodies to the Fc portion of IgG prevent this negative Fc-signalling, provided that these antibodies do not emit Fc signals. Prevention of Fc signals leads to augmented antibody responses to self and foreign antigens, and reduces the requirement for T cells by 10- to 100-fold in T cell-dependent antibody responses. In ELISA assays, peptides from conserved portions of the glycoproteins, HIV-1 gp120 or gp41 from HIV-1 and HIV-2 bind to the Fc portion of IgG, but do not bind the F(ab')2 portion of IgG. HIV-derived peptides, which bind to the Fc portion of IgG, augment the antibody-forming cell response to single-stranded (ss)DNA. The spontaneous response to ssDNA using spleen cells from young mice, and the response in the presence of exogenous DNA using spleen cells from old mice, are augmented to the greatest extent. These results demonstrate that HIV peptides bind to the Fc portion of IgG and augment immune responses to DNA; they suggest the possibility that blockade of the Fc portion of IgG antibodies is associated with a reduction in Fc-mediated regulation of anti-self responses. Blockade of regulatory Fc-signalling may account for increased circulating immunoglobulins and autoantibodies in clinical AIDS.