Human monoclonal antibodies to the V3 loop of HIV-1 with intra- and interclade cross-reactivity
Gorny, M.K.; VanCott, T.C.; Hioe, C.; Israel, Z.R.; Michael, N.L.; Conley, A.J.; Williams, C.; Kessler, J.A.; Chigurupati, P.; Burda, S.; Zolla-Pazner, S.
Journal of Immunology 159(10): 5114-5122
1997
ISSN/ISBN: 0022-1767 PMID: 9366441 Document Number: 479586
Five human anti-V3 monoclonal antibodies (mAbs) were generated from Ab-producing cells derived from the blood of HIV-1-infected individuals from North America and selected using the V3 peptide of a divergent clade B isolate, HIVRF. The anti-V3RF mAbs were mapped to a cluster of 3 overlapping epitopes present in the KSITKGP sequence located in the hypervariable region on the N-terminal side of the V3 loop. Broad immunochemical cross-reactivity was noted when the mAbs were tested for binding to V3 peptides derived from 4 clade A viruses, 9 clade B viruses, and 2 clade C viruses. These results demonstrate antigenic relatedness in the V3 regions of these 3 HIV-1 clades. Affinities determined by surface plasmon resonance were higher for recombinant gp120 than for V3 peptides, suggesting that these mAbs recognize both linear and conformationally dependent epitopes of the V3 loop. Two of the mAbs neutralized 4 clade B T cell line-adapted and primary isolates with varying degrees of potency. The 2 neutralizing mAbs were the most cross-reactive with V3 peptides from several clades, had the highest affinity for V3RF and V3MN, and stained HIV-infected cells. The data suggest that cross-reactivity, affinity, cell surface staining, and neutralizing activity are characteristics that describe an optimal fit between Ag and Ab. These results also demonstrate that the V3 peptides representing the sequence of several clade A, B, and C viruses share antigenic features that are recognized by the human immune response, a finding that suggests that cross-clade immunity to HIV-1 may be inducible by HIV-1 vaccines.