The reactivities of HIV-1+ human sera with solid-phase V3 loop peptides can be poor predictors of their reactivities with V3 loops on native gp120 molecules.

The binding of HIV-1+ human serum antibodies to solid phase-adsorbed V3 loop peptides from the IIIB, SF-2, and MN isolates was compared with the abilities of the same peptides to inhibit binding of the sera to the homologous or heterologous native gp120 molecules. The reactivities of the sera with the solid-phase peptides were found to be poor predictors of the potencies of the peptides as competitors in solution for antibody binding to the V3 loop in situ. Furthermore, the extent of cross-reaction of HIV-1+ human serum antibodies with the three V3 peptides in solid-phase assays was potently influenced by the presence or absence of nonionic detergent. Because the use of solid-phase V3 peptide assays is widespread, and there is no consensus on the use or omission of detergent, there is considerable potential for confusion. These factors should be considered when interpreting data derived from V3 peptide serology when this method is used to dissect the human immune response to HIV-1 infection. It is also shown in quantitative studies of HIV-1+ serum antibody binding to homologous and heterologous gp120s that the general anti-gp120 antibody response is significantly "type specific" for the homologous gp120.