Figure 7.

Monoclonal antibodies (MAbs) raised to E-gp120. (A) Epitope specificity-neutralizing activity relationships. Anti-E-gp120 MAbs frequently display binary E-288–306 and E-421–433 binding. Binding of E-288–306 and E-421–433 by 17 MAbs was measured. Plotted are band intensities (in arbitrary volume unit, AVU) of the adducts formed by individual MAbs. Cyan quadrant contains MAbs with adduct densities at least 4-fold greater than the background mean band intensity of adducts formed by the irrelevant control E-peptide probes (binary peptide binding MAbs). Yellow quadrant contains monoreactive MAbs to E-288–306. Red symbols denote MAbs that neutralized subtype C strain 97ZA009 (IC₅₀ < 20 μg/mL); black symbols, non-neutralizing MAbs. Number in parentheses corresponds to the MAbs in the quadrant. (B) Binary epitope BCR-immunogen recognition model. E-gp120 binds BCR nucleophiles (Nu) covalently, releasing a large amount of energy that eliminates the physiological restriction on differentiation of innate CD4BD^core-specific B cells. Concomitant CDR binding by the 2nd E-gp120 epitope also counteracts negative B cell signaling. (C) Expanded view of V_H FR-cavity fitted with the solid white object deduced by crystallography. Cyan, V_H FR residues; green, V_H CDR2 residues. Yellow line connects atoms that can form a nucleophilic diad by serving as the proton donor–acceptor pair (V_H T70 Oγ; V_H T70 carbonyl O). Panels (A) and (C) from reference Nishiyama et al. (2009).