Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition

Abstract

PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino acid sequence of this antibody binding site was demonstrated by multiple length scanning to be five to eight amino acids in length: (G)PGRAF(VT), i.e. amino acids 312-319. A peptide (Neu 21) containing this binding site for human antibodies (KSIRIQRGPGRAFVTIG) was synthesized and shown to induce HTLV-III B cell fusion-inhibiting antibodies in rabbits and mice. Antibodies binding to this HTLV-III B/LAV-1-specific peptide were shown to be primarily of the IgG 1 subclass, appeared within 6 months after HIV-1 antibody seroconversion in six out of 14 men studied, and persisted throughout the follow-up period of 10-24 months. The other eight seroconverting men did not develop antibodies to Neu 21 during the observation period. The appearance of antibodies to Neu 21 paralleled the capacity of the serum to inhibit HTLV-III B in cell fusion. HIV-1-infected men with Kaposi's sarcoma exhibited a similar frequency of antibodies to the synthetic peptide Neu 21 (14 out of 39, 36%) as asymptomatic HIV-1-infected men (112 out of 319, 35%). Adults with Pneumocystis carinii pneumonia had a significantly lower frequency (11 out of 78, 14%) of antibodies to Neu 21. Similarly, a low prevalence of antibodies to Neu 21 (8 out of 43, 19%) was observed among symptomatic HIV-1-infected children.