Human immunodeficiency virus V3 peptide-reactive antibodies are present in normal HIV-negative sera.
A structural relation between consensus sequences of the portion of HIV-1 gp120 involving the V3 loop (V3 peptide) and the variable domains of human immunoglobulin members of the VH-III gene family was proposed to trigger an imbalance of the idiotypic network during the course of HIV infection. Thus, the repertoires of immunoglobulins in healthy individuals should contain antigenic determinant(s) complementary to particular V3 loop epitope(s). In this study we investigated the specific binding to the V3 peptide of antibodies present in sera of HIV-positive and of clinically normal HIV-negative subjects. Two groups of HIV-positive sera differing in antibody titers to V3 peptide, arbitrarily referred here as high- and low-reactive HIV-positive sera, were distinguished on the basis of an ELISA. Antibodies were affinity purified on V3 peptide and their titers in both HIV-negative and low-reactive HIV-positive sera were nearly superimposable and much lower than the titers of those from high-reactive HIV-positive sera. Also, the quality of the two groups of antibodies differed: much higher amounts of soluble V3 peptide were needed to partly compete the binding of antibodies from HIV-negative sera to insoluble V3 peptide as compared with those from HIV-positive sera, suggesting that the latter had higher affinity for V3 peptide. All of the affinity-purified antibodies bound poorly to unrelated peptides, even to those sharing sequence similarity with the V3 peptide. The present observations suggest that in HIV infection antigen-driven affinity maturation of preimmune immunoglobulins with idiotypes complementary to V3 epitope(s) participating in physiological autoreactivity might be at work.
Metlas
R
R
R&D Division, Diapharm, Belgrade, Yugoslavia.
Trajkovic
D
D
Srdic
T
T
Veljkovic
V
V
Colombatti
A
A
D000595:Amino Acid Sequence; D000915:Antibody Affinity; D000937:Antigen-Antibody Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*
D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007130:Immunoglobulin Idiotypes; D010446:Peptide Fragments