Properties of a neutralizing antibody that recognizes a conformational form of epitope ERDRD in the gp41 C-terminal tail of human immunodeficiency virus type 1.
The possibility that epitopes from the C-terminal tail of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) are exposed the surface of the virion has long been contentious. Resolution of this has been hampered by the absence of any neutralizing monoclonal antibodies, but we have recently epitope-purified a neutralizing polyclonal IgG specific for one of the putative gp41 tail epitopes, (746)ERDRD(750). This was obtained from mice immunized parenterally with a plant virus chimera expressing residues 731-752 from the gp41 tail. The ERDRD epitope is highly conformational and is conserved in 81% of B clade viruses. Here, it is shown that this polyclonal ERDRD-specific IgG is highly potent, with an affinity of 2.2x10(8) M(-1), and a neutralization rate constant (-K(neut)) of 7.8x10(4) M(-1) s(-1) that exceeds that of nearly all other known HIV-1-neutralizing antibodies. ERDRD-specific IgG gave 50% neutralization at 0.1-0.2 microg/ml and 90% neutralization at approximately 3 microg/ml. It also neutralized virus that was already attached to target cells, and this and other data suggest that it neutralized by inhibiting a virion event that precedes the fusion-entry process. Consistent with this conclusion was the finding that neutralizing amounts of ERDRD-specific IgG did not inhibit the attachment of free virus to target cells. ERDRD-specific IgG was also cross-reactive and neutralized all but one of six B clade T cell line-adapted strains tested.
Cleveland
S M
SM
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK Axis Genetics plc, Babraham, Cambridge CB2 4AZ, UK.
Jones
T D
TD
Dimmock
N J
NJ
D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins; D020349:Surface Plasmon Resonance
D000939:Epitopes; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins