Effects of oligomerization on the epitopes of the human immunodeficiency virus type 1 envelope glycoproteins

To understand the differential expression of epitopes on monomeric and olig omeric forms of the envelope glycoproteins, nine human monoclonal antibodie s (mAbs) were derived from the cells of human immunodeficiency virus-infect ed subjects by selection with soluble oligomeric gp140 (o.140). These nine mAbs and 12 human mAbs selected with V3 peptides, viral lysates, and rgp120 , specific for the V2, V3, C5, CD4-binding domain (CD4bd), and gp41, were t ested in a binding assay to compare the exposure of these regions on monome ric gp120 or gp41 and on o.140 None of the 21 mAbs were oligomer specific. However, mAbs to vs and CD4bd were oligomer sensitive," whereas mAbs to V2 and the distal epitope of C5 tended to be "monomer sensitive" (i.e., to rea ct better with the oligomer or monomer, respectively) The majority of anti- gp41 mAbs reacted similarly with monomer and oligomer. Although the uncleav ed o.140 used in this study differs from the cleaved gp120/41 oligomer foun d on the native virus particle, these results suggest that new epitopes are not introduced by oligomerization of viral envelope proteins, that such ol igomer-specific epitopes, if they exist, are not highly immunogenic, and/or that they are not efficiently selected using soluble o.140, (C) 2000 Acade mic Press.