A defined conformational epitope from the C4 domain of HIV type 1 glycoprotein 120: Anti-cyclic C4 antibodies from HIV-positive donors magnify glycoprotein 120 suppression of interleukin 2 produced by T cells

The C4 domain of HIV gp120 plays a functionally vital role in the binding o f gp120 to CD4 receptors on target cells. Antibodies to an 11-amino acid cy clic C4 peptide were obtained from immunized rabbits and from the serum of an HIV-positive human and were found to recognize gp120 bound to CD4. Anti- cyclic C4 antibodies magnified gp120-induced suppression of IL-2 produced b y T cells in vitro. Rabbit antibodies to the 11-amino acid linear C4 peptid e did not recognize gp120 in the free state or when bound to CD4. These res ults indicate that a conformationally defined, highly conserved epitope in the gp120 C4 region remains exposed on CD4 binding. Naturally occurring ant ibodies to this epitope can augment gp120-induced immunosuppression and may contribute to disease progression.