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 oligomeric forms of the envelope glycoproteins, nine human monoclonal antibodies (mAbs) were derived from the cells of human immunodeficiency virus-infected 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 tested in a binding assay to compare the exposure of these regions on monomeric gp120 or gp41 and on o.140. None of the 21 mAbs were oligomer specific. However, mAbs to V3 and CD4bd were "oligomer sensitive," whereas mAbs to V2 and the distal epitope of C5 tended to be "monomer sensitive" (i.e., to react better with the oligomer or monomer, respectively). The majority of anti-gp41 mAbs reacted similarly with monomer and oligomer. Although the uncleaved o.140 used in this study differs from the cleaved gp120/41 oligomer found on the native virus particle, these results suggest that new epitopes are not introduced by oligomerization of viral envelope proteins, that such oligomer-specific epitopes, if they exist, are not highly immunogenic, and/or that they are not efficiently selected using soluble o.140.
Gorny
M K
MK
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
VanCott
T C
TC
Williams
C
C
Revesz
K
K
Zolla-Pazner
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D054299:env Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1