Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1

• Published in: Journal of general virology 1991-10, Vol.72 (10), p.2519-2526
• Main Authors: Langedijk, J. P. M, Back, N. K. T, Durda, P. J, Goudsmit, J, Meloen, R. H
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Animals; Antibodies, immunoglobulins; Antibodies, Monoclonal - immunology; Antibody Specificity; Biological and medical sciences; Chromatography, High Pressure Liquid; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; Mice; Molecular immunology; Molecular Sequence Data; Monoclonal antibodies; Neutralization Tests; Peptide Fragments - immunology; Protein Conformation
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-72-10-2519

1 Central Veterinary Institute, P.O. Box 65, 8200 AB Lelystad 2 Human Retrovirus Laboratory, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands and 3 DuPont, Biotechnology Systems, North Billerica, Massachusetts, U.S.A. Monoclonal antibodies (MAbs) raised against a 15-mer peptide representing the centre of the principal neutralization domain of human immunodeficiency virus type 1 (strain BH10) showed wide variations in neutralizing activity against the homologous strain. The nature of this difference in neutralizing activity was studied by measuring antibody concentration, their affinity for peptide and specificity, by reaction with peptides which differed in the extent of sequence overlap, length and the presence of single amino acid replacements. All MAbs bound to approximately the same region in the principal neutralization domain, within the sequence RIQRGPGRAFV. The peptides with which each antibody was able to react differed by only a few amino acids. The neutralizing activity of each MAb preparation was related to its afinity and concentration; the affinity is related in part to the fine structure of the epitope recognized. MAbs with high affinity for the peptide tended to react only with peptides in which amino acid replacements did not affect the -turn potential of the peptide, whereas the reactivity of MAbs with low affinity was relatively insensitive to amino acid replacements affecting the -turn potential. Received 26 March 1991; accepted 28 June 1991.