title: Comparison and fine mapping of both high and low neutralizing monoclonal antibodies against the principal neutralization domain of HIV-1.
abstract: Monoclonal antibodies raised against viral lysate of HIV-1 (strain LAV-1) and against recombinant gp 160 of HIV-1 (strain HTLV IIIB) which neutralized HIV-1 in a type specific manner were mapped with the aid of peptides (Pepscan analysis). Each of these monoclonal antibodies bound to peptides located on the principal neutralizing domain (PND) of HIV-1. We found that the antigenic sites of the MAbs described in this paper are represented by linear peptides of at least 10 amino acids long. The affinity of the MAbs is high for these peptides and in the same order of magnitude as for native gp 160. The fine mapping of the epitopes may reflect structural features of the PND, for instance which amino acid side chains are exposed and which are buried in the protein. Furthermore the fine mapping of the epitopes explained the HIV type-specific neutralizing activity of the MAbs. Antibodies that bound to the tip of the loop (amino acids QRGPGRAF) have a higher neutralizing activity than antibodies that bound to amino acids towards the N-terminal side of the loop (amino acids KSIRI). Furthermore, MAbs that bound to virtually the same amino acids on the tip of the loop (amino acids IQRGPGRAF and RGPGRAFV) had different neutralizing activities due to different affinities for native gp 160. These data reveal that neutralizing activity not only is determined by the affinity of an antibody to the neutralizing site but also by its fine binding specificities to the V 3 loop of gp 120.
authors.affiliation: Central Veterinary Institute, Lelystad, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: Langedijk
authors.forename: N K
authors.initials: NK
authors.lastname: Back
authors.forename: E
authors.initials: E
authors.lastname: Kinney-Thomas
authors.forename: C
authors.initials: C
authors.lastname: Bruck
authors.forename: M
authors.initials: M
authors.lastname: Francotte
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: R H
authors.initials: RH
authors.lastname: Meloen
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D010446:Peptide Fragments; D011498:Protein Precursors