Two Are Better than One

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Science  12 Nov 2010:
Vol. 330, Issue 6006, pp. 891
DOI: 10.1126/science.330.6006.891-b

Two hallmarks of antibody recognition are high binding affinity and the ability of the two antibody arms to bind copies of the same region of an antigen. Eliciting broadly neutralizing antibodies by vaccination is a key therapeutic goal in fighting HIV. One conundrum, however, is that a critical HIV antibody target, the viral spike (gp140), is found at a relatively low density on the viral surface, and so the ability of an antibody to bind gp140 with both arms is unlikely. Such monovalent binding would probably lead to less-effective viral neutralization. To better understand antibody binding to gp140, Mouquet et al. analyzed 134 distinct neutralizing gp140 antibodies and found that 75% of these were polyspecific, in contrast to 17% of control antibodies. They found that these polyreactive antibodies were able to bind gp140 with high affinity and also to a second viral structure with low affinity. B cell development favors the production of antibodies with a single specificity; thus, one explanation for why broadly neutralizing antibodies are so hard to elicit in response to HIV may be because polyreactive antibodies are relatively rare.

Nature 467, 591 (2010).

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