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Scanlan, CN; Pantophlet, R; Wormald, MR; Saphire, EO; Calarese, D; Stanfield, R; Wilson, IA; Katinger, H; Dwek, RA; Burton, DR; Rudd, PM.
(2003): The carbohydrate epitope of the neutralizing anti-HIV-1 antibody 2G12
In: Axford, JS. editors(s). GLYCOBIOLOGY AND MEDICINE; ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY535: 205-218. (ISBN: 0-306-47782-3)

Abstract:: 12 is a broadly neutralizing human monoclonal antibody against human immunodeficiency virus type-1 (HIV-1) that has previously been shown to bind to a carbohydrate-dependent epitope on gp120. Here, site-directed mutagenesis and carbohydrate analysis were used to define further the 2GI2 epitope. Alanine scanning mutagenesis showed that elimination of the N-linked carbohydrate attachment sequences associated with residues N295, N332, N339, N386, and N392 by N --> A substitution produced significant decreases in 2G12 binding affinity to gp120(JR-CSF). The mutagenesis studies provided no convincing evidence for the involvement of gp120 amino acid side chains in 2GI2 binding. Antibody binding was inhibited when gp120 was treated with Aspergillus saitoi mannosidase, Jack Bean mannosidase, or endoglycosidase H, indicating that Manalpha1 --> 2Man-linked sugars of oligomannose glycans on gp120 are required for 2G12 binding. Consistent with this finding, the binding of 2GI2 to gp120 could be inhibited by monomeric mannose but not by other hexoses. The data presented here suggests that the most likely epitope for 2GI2 is formed from a specific cluster of mannose residues on the outer face of gp120, with the other glycans playing an indirect role in maintaining epitope conformation.
Authors BOKU Wien:: Katinger Hermann
Find related publications in this database (using NML MeSH Indexing): Alanine - metabolism; Animals -; Antibodies - immunology; Carbohydrate Metabolism -; Carbohydrates - immunology; Epitopes - immunology; Glycoside Hydrolases - metabolism; HIV Envelope Protein gp120 - genetics; HIV-1 - immunology; Humans -; Mutation -; Protein Binding -; Protein Structure, Tertiary -