Since the number of existing neutralizing mAbs with a relatively broad neutralization profile is very limited, and those described to date, with the exception of the Walker et al MAbs were isolated from clade B virus-infected donors, we undertook the task of isolating new human mAbs from HIV-1-infected donors. Our primary aims were: i) to isolate novel MAbs with cross-clade neutralizing activity from non-B clade donors; ii) to analyze the memory B cell repertoire in a representative panel of predominantly non-B clade-infected individuals. By using an improved memory B cell immortalization method [41] , combined with highthroughput parallel screening with a panel of recombinant Envbased antigens, we isolated a panel of 58 human mAbs which we have characterized with regard to epitope specificity and breadth of neutralization. We have more fully characterized three mAbs from this panel that demonstrated complementary and relatively broad cross-clade neutralizing profiles that target the gp120 CD4bs and the V3 crown, and the gp41 heptad repeat 1 (HR-1).