title: Binding of HIV-1 gp120 to an anti-V3 loop antibody reveals novel antigen-induced epitopes.
abstract: Antigen association to its corresponding binding site in the immunoglobulin molecule can elicit conformational rearrangements, generating novel epitopes termed metatopes. Such metatopes were characterized for the immunocomplex between the AIDS virus envelope protein, gp120, and M77, a mAb directed against the V3 loop. Five novel mAbs were described (GV1, GV3, GV7, GV8, and GV12). These mAbs were found to bind epitopes harbored in the M77 Fab fragment. Binding to the epitopes was shown to require the complexation of Fab with its antigen. The degree of this antigen requirement was found to be variable for the different mAbs and also for the state of IgG fragmentation. Binding of GV12 to its antigen increased the affinity of M77 for gp120. Moreover, in the presence of GV12, M77 acquired extended cross-reactivity for a second gp120 variant, namely BaL. These results could indicate a novel approach towards improving the performance of anti-HIV antibodies.
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Science, Tel Aviv University, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Denisova
authors.forename: J
authors.initials: J
authors.lastname: Zwickel
authors.forename: J M
authors.initials: JM
authors.lastname: Gershoni
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010446:Peptide Fragments