Human immunodeficiency virus V3 peptide-reactive antibodies are present innormal HIV-negative sera

A structural relation between consensus sequences of the portion of HIV-1 g p120 involving the V3 loop (V3 peptide) and the variable domains of human i mmunoglobulin 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 antib odies 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-positiv e sera, were distinguished on the basis of an ELISA, Antibodies were affini ty purified on V3 peptide and their titers in both HIV-negative and low-rea ctive 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 pe ptide were needed to partly compete the binding of antibodies from HIV-nega tive 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 obser vations suggest that in HIV infection antigen-driven affinity maturation of preimmune immunoglobulins with idiotypes complementary to V3 epitope(s) pa rticipating in physiological autoreactivity might be at work.