The majority of neutralizing Abs in HIV-1-infected patients recognize linear V3 loop sequences. Studies using HIV-1MN multiple antigenic peptides

Abstract

Multiple antigenic peptides (MAP) comprising eight synthetic peptides corresponding to the V3 loop of HIV-1MN or HIV-1IIIB linked to a lysine core were used to characterize the humoral Ab response of HIV-1-infected patients against this domain. One hundred percent of the tested sera from HIV-1-infected European patients reacted significantly with the HIV-1MN V3 loop MAP. Most, but not all, sera also reacted against the HIV-1IIIB V3 loop MAP, albeit with low titers. The in vitro neutralization capacity of the patients' sera against HIV-1MN or HIV-1IIIB infection were tested. All sera showed significant neutralizing titers against HIV-1MN, in comparison with the low (when detectable) neutralizing titers against HIV-1IIIB. Competition assays revealed that the majority of HIV-1MN-neutralizing Abs in patients' sera react with the V3 loop peptides. Only a small fraction of the total neutralizing capacity, presumably specific for other neutralizing epitopes, could not be adsorbed with HIV-1MN V3 loop peptides. The V3 loop peptides could also compete for the binding of Abs in patients' sera mediating Ab-dependent cellular cytotoxicity (ADCC) of HIV-1MN infected cells, inhibiting 30 to 80% of the ADCC activity. Finally, the HIV-1MN V3 loop MAP, when used as immunogen in the presence of RIBI adjuvant without a carrier protein, elicited Abs able to neutralize HIV-1MN (but not HIV-1IIIB) and to initiate ADCC of HIV-1MN-infected cells. This neutralizing and ADCC activity, mediated by V3MN-specific rabbit Abs, could be totally absorbed by V3MN loop peptides.