Human monoclonal antibodies against the HIV-1 envelope glycoproteins are useful tools in the structural and functional analysis of the viral envelope and have crucial roles in guiding the design of prophylactic anti-HIV vaccines. Despite a huge expansion of HIV-1 subtype-C worldwide, the clade-C viruses remain to be one of the least studied subtypes especially in terms of HIV-1 neutralizing antibodies. Using the rationale from previous studies showing that viruses with GPGQ residues at the tip of the V3 crown of the HIV-1 envelope induce potent and cross reactive NAbs as compared to viruses with GPGR motif, we generated here three anti-V3 mAbs from Indian donors presumably infected with subtype-C viruses bearing GPGQ at the V3 crown [42] . The functional analysis of the Abs generated reveals a potent neutralization potential with tier 1 viruses while such activity was limited with the tier 2 viruses tested. The anti-V3 Abs were selected from EBV-transformed B-cell cultures of 33 HIV-1 infected antiretroviral drug naïve patients using V3C-CTB fusion protein [47] . The advantage of using a conformationally constrained instead of a linear V3 peptide for selection of mAbs from cultures or as animal immunogens has been previously demonstrated [36, 41, [48] [49] [50] . We found 1-25% (mean = 6%) of the transformed wells positive for binding with V3C-CTB in the first screening. The characteristic nature of the B-cells from HIV-1 infected subjects and the conditions used to immortalize them apparently affects the number and type of Ab-producing cell lines that grow out [51] . The overall positive percentage of Ab secreting culture wells was relatively good and could be attributed to the high titers of anti-V3 Ab reactivity of the corresponding plasma [28] . In contrast to a high percentage of positive secretors in the initial screening, we were able to stabilize only three (277, 903 and 904) anti-V3 Ab producing B-cell clones. This loss could be in part due to the outgrowth of the non-secretor B cells over the secretor B cells in subsequent steps of secondary screening, cell fusion and dilution cloning process. Moreover, the B cells from HIV-1 infected patients are mostly dysfunctional and polyclonally activated [52] , and such properties have been associated with a low persistence of EBV infectivity [51, 53, 54] .