Skip to main content
. Author manuscript; available in PMC: 2011 Aug 13.
Published in final edited form as: Science. 2010 Jul 8;329(5993):811–817. doi: 10.1126/science.1192819

Figure 6. Somatic maturation and VRC01 affinity.

Figure 6

Hypermutation of the variable domain during B cell maturation allows for the evolution of high affinity antibodies. Interestingly, this enhancement to affinity occurs principally through the alteration of non-contact residues, which appear to reform the genomic contact surface from affinity too low to measure to a tight (nM) interaction. (A) Effect of genomic reversions. The VH- and VΚ-derived regions of VRC01 were reverted to the sequences of their closest genomic precursors, expressed as immunoglobulins and tested for binding as VH- and VΚ-revertants (gHgL), as a VH-only revertant (gH), or as a VΚ-only revertant (gL) to either the gp120 construct used in crystallization (93TH057) or to a stabilized HXBc2 core (22). (B) Maturation of VRC01 and correlation with binding. Affinity measurements for the 19 VRC01 mutants created during the structure-function analysis of VRC were analyzed in the context of their degree of affinity maturation. Significant correlations were observed, with extrapolation to VH- and VΚ-revertants suggesting greatly reduced affinity for gp120. (C) Maturation of VRC01 and effect on HIV-1 gp120 affinity. Cryo-electron microscopy density (pink) corresponding to the unliganded state of the trimeric HIV-1 viral spike (50) is shown in complex with the antigen-binding fragment of VRC01. The Cα-backbone ribbon is displayed for gp120s (red) and VRC01 grey. With VRC01, the molecular surface is shown for residues altered from the closest VH- and VΚ-genomic precursor sequences and colored gray to green depending on the effect of the reversion on gp120 affinity, with gray indicating small effects and green larger ones.