The effect of sCD4 on the binding and accessibility of HIV-1 gp41 MPER epitopes to human monoclonal antibodies.
Two human monoclonal anti-HIV-1 antibodies, 2F5 and 4E10, were utilized to investigate the accessibility and conservation of gp41 MPER epitopes on five different clades of HIV-1 in the absence and presence of sCD4. The binding of human monoclonal antibodies (mAbs) to HIV-1 was dependent upon the virus clade. Soluble CD4 significantly increased the accessibility of gp41 MPER-binding epitopes on several isolates that previously showed little or no binding with 2F5 and 4E10 mAbs as determined by a modified ELISA-based virus capture assay and surface plasmon resonance. Studies on the relationship between virus binding and neutralization in a TZM-bl pseudovirus assay indicated that in most cases, mAbs that exhibited neutralization also bound the virus. However, neither binding per se nor the total envelope content per virion was a predictor of neutralization. The hidden or conformational gp41 MPER epitopes unmasked by sCD4 may provide additional targets for vaccine design.
Henry M. Jackson Foundation for the Advancement of Military Medicine, 1600 East Gude Drive, Rockville, MD, 20850, USA.
Kristina K
KK
Peachman
Lindsay
L
Wieczorek
Victoria R
VR
Polonis
Carl R
CR
Alving
Mangala
M
Rao
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D057134:Antibodies, Neutralizing / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral; D015483:HIV Antibodies / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D012995:Solubility; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1