Human immunodeficiency virus type 1-neutralizing monoclonal antibodies which react with p17 core protein: characterization and epitope mapping

Abstract

Monoclonal antibodies (MAbs) to human immunodeficiency virus type 1 were produced. Two antibodies reacted with the 17-kilodalton core protein (p17) of the virus and with its polyprotein precursor. To various degrees, each MAb neutralized infection by the cell-free virus. With a series of sequential overlapping hexapeptides which represent the p17 gene product, the epitopes identified by the MAbs were defined. The epitopes localize to overlapping regions near the amino terminus of the protein. Soluble synthetic peptides which span the antibody-binding sites of interest were demonstrated to competitively inhibit the reactivity of p17 MAbs, thus confirming the location of virus-neutralizing sites within the core protein.

Fine Molecular Specificity of Linear and Assembled Antibody Binding Sites in HIV‐1 p24

“…In Ihe case of LH 104-1 the hexapeptide scan had a special profile in ihat none of the pepiides on either side of this single peak gave any reaction. Such restricted profiles have also been reported by others [34], We assume ihat in this case there are ralher slringent stereochemical requirements for antibody recognition. The anlibody LH 104-1 reacted wiih p24 in Western biol.…”

Major antigenic domain recognized by monoclonal antibodies maps within the carboxy‐terminal moiety of a recombinant human immunodeficiency virus‐1 p24 protein

“…The definition of the antigenic structure of HIV-1 capsid proteins has been the subject of recent investigations [Coates et al, 1987;Ferns et al, 1987;Di Marzo-Veronese et al, 1985;Niedrig et al, 1988;Spence et al, 1989a, b;Niedrig et al, 1989, Tersmette et al, 1989Papsidero et al, 1989;Argos, 19891. Results described in this paper indicate the presence of a highly immunogenic domain on the carboxyterminal moiety of a recombinant p24 molecule (r-p39). Within the maximal extension so far determined for such a domain (amino acids 168-208), we mapped a minimal number of four distinct B cell epitopes, of which three clustered in a single dominant determinant.…”

Strategies for mapping and imitating viral B-cell epitopes

“…Similarly, a minimum binding site for an antibody can be identified by creating panels of peptides sequentially truncated from the amino and/or carboxylic terminus. Synthetic peptides have been employed to localize antigenic determinants recognized by neutralizing mAbs to foot-and-mouth disease virus (Meloen et al, 1987), rhinovirus- (Sherry et al, 1986), human immunodeficiency virus (Papsidero et al, 1989), murine coronaviruses (Luytjes et al, 1989) and a type-restricted epitope on human papillomavirus type 16 (Cason et al, 1989). Whilst peptide mapping techniques are particularly useful for identifying epitopes recognized by mAb or polyclonal antisera derived from hyperimmune animals, the application of this technology for identifying epitopes recognized by antibodies in human sera can often prove to be problematic due to high levels of antibody binding to peptides per se.…”