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A broad range of mutations in HIV-1 neutralizing human monoclonal antibodies specific for V2, V3, and the CD4 binding site.
- Source :
-
Molecular immunology [Mol Immunol] 2015 Aug; Vol. 66 (2), pp. 364-74. Date of Electronic Publication: 2015 May 18. - Publication Year :
- 2015
-
Abstract
- The HIV vaccine-induced neutralizing antibodies (Abs) display low rates of mutation in their variable regions. To determine the range of neutralization mediated by similar human monoclonal Abs (mAbs) but derived from unselected chronically HIV-1 infected subjects, we tested a panel of 66 mAbs specific to V3, CD4 binding site (CD4bs) and V2 regions. The mAbs were tested against 41 pseudoviruses, including 15 tier 1 and 26 tier 2, 3 viruses, showing that the neutralization potency and breadth of anti-V3 mAbs were significantly higher than those of the anti-CD4bs and anti-V2 mAbs, and only anti-V3 mAbs were able to neutralize some tier 2, 3 viruses. The percentage of mutations in the variable regions of the heavy (VH) and light (VL) chains varied broadly in a range from 2% to 18% and correlated moderately with the neutralization breadth of tier 2, 3 viruses. There was no correlation with neutralization of tier 1 viruses as some mAbs with low and high percentages of mutations neutralized the same number of viruses. The electrostatic interactions between anti-V3 mAbs and the charged V3 region may contribute to their neutralization because the isoelectric points of the VH CDR3 of 48 anti-V3 mAbs were inversely correlated with the neutralization breadth of tier 2, 3 viruses. The results demonstrate that infection-induced antibodies to CD4bs, V3 and V2 regions can mediate cross-clade neutralization despite low levels of mutations which can be achieved by HIV-1 vaccine-induced antibodies.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antibodies, Neutralizing chemistry
Antibodies, Neutralizing immunology
Antibodies, Viral chemistry
Antibodies, Viral immunology
Binding Sites
CD4 Antigens chemistry
CD4 Antigens immunology
Gene Expression
HIV Envelope Protein gp120 chemistry
HIV Envelope Protein gp120 immunology
HIV Infections blood
HIV Infections immunology
HIV Infections virology
HIV-1 chemistry
HIV-1 genetics
HIV-1 immunology
Humans
Hybridomas chemistry
Hybridomas immunology
Immunoglobulin Variable Region chemistry
Immunoglobulin Variable Region immunology
Protein Binding
Antibodies, Neutralizing genetics
Antibodies, Viral genetics
CD4 Antigens genetics
HIV Envelope Protein gp120 genetics
Immunoglobulin Variable Region genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 66
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 25965315
- Full Text :
- https://doi.org/10.1016/j.molimm.2015.04.011