Several studies have questioned the existence of individual broadly neutralizing antibody specificities as part of a normal immune response to HIV-1 infection. In this respect, b12 was isolated from a phage library, while 2F5, 4E10 and 2G12, although isolated from memory B cells, do not appear to have a counterpart in human sera [22] . In a recent study, Nussenzweig and coworkers used trimeric gp140 to isolate antigen-binding memory B cells from which 500 antibody sequences were retrieved by single-cell PCR [62] . Surprisingly, although the B cell donors had broadly neutralizing serum activity, none of the mAbs isolated had this property. This raised the possibility that broad serum neutralizing activity results from multiple clonal responses each of unique epitope specificity but restricted breadth of viral strain recognition. However, an alternative interpretation might be that since available recombinant trimeric antigens vary in structure, the 'bait' used for B cell isolation was not optimal for enriching those secreting neutralizing antibodies. Our results indicate that monoclonal antibodies with a limited spectrum of neutralizing activity can be easily isolated, while those with a broad pattern of cross-clade reactivity are rare, in line with the study of Walker et al [40] and consistent with inferences from serum neutralization specificity mapping analyses [21] . In this respect our study demonstrates the feasibility of the EBV immortalization method, which is limited only by the size of the blood samples obtained (20-50 ml of peripheral blood). The characterization of the specificity and neutralizing activity of this new panel of human mAbs reveal some interesting features of the human antibody response to HIV-1 within a population of HIV-1-infected donors. First, most of the gp120-specific mAbs showed neutralizing activity (37 out of 58), indicating that they bind to sites available on the functional Env trimer. The selection of a highpercentage of trimer binding specificities may be a consequence our use of trimeric Env antigens during the screening of the EVB-B cell supernatants. The second aspect relates to gp41-specific antibodies, which, with a few remarkable exceptions, were not neutralizing. Interestingly the non-neutralizing antibodies bound gp41 in the context of the recombinant trimer, whereas the most effective neutralizing mAbs bound to gp41 fusion intermediates.