MAb HJ16, derived from a donor infected with clade C, has a unique neutralization profile with potent and selective neutralization of multiple Tier-2 pseudoviruses ( Figure 1B and Figure 2 ). When compared with the CD4bs-specific mAb b12 for gp120 binding, HJ16 showed similar binding curves ( Figure 3A ) and inhibited to a comparable extent the binding of gp120 to solid-phase sCD4 ( Figure 3B , IC 50 values of 1.57 and 1.16 mg/ml, respectively). However, cross-competition analysis of HJ16 and b12 for binding to gp120 revealed incomplete heterologous inhibition, with plateau values of approximately 80% ( Figure 3C-D) . These results suggest that HJ16 and b12 recognize related but non-overlapping CD4bsproximal epitopes. To further characterize HJ16 specificity we measured its binding to two YU2 gp120 mutants: the D368R mutant, which is not bound by CD4 or CD4bs-specific mAbs [21] and the I420R mutant, which is not recognized by CD4i-specific mAbs [62] . As already reported, b12 bound the I420R CD4i mutant, but failed to recognize the D368R CD4bs mutant. By contrast, HJ16 bound both mutants and indeed bound better to the D368R CD4bs mutant compared to the wild-type molecule ( Figure 3E-F) . Attempts to map the epitope by Pepscan analysis using overlapping linear peptides were unsuccessful (not shown), consistent with HJ16 recognition of a discontinuous epitope.