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

Abstract

The C4 domain of HIV gp120 plays a functionally vital role in the binding of gp120 to CD4 receptors on target cells. Antibodies to an 11-amino acid cyclic 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 by T cells in vitro. Rabbit antibodies to the 11-amino acid linear C4 peptide did not recognize gp120 in the free state or when bound to CD4. These results indicate that a conformationally defined, highly conserved epitope in the gp120 C4 region remains exposed on CD4 binding. Naturally occurring antibodies to this epitope can augment gp120-induced immunosuppression and may contribute to disease progression.