Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120
Open Access
- 27 June 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (30), E2083-E2090
- https://doi.org/10.1073/pnas.1208984109
Abstract
A large number of anti–HIV-1 antibodies targeting the CD4-binding site (CD4bs) on the envelope glycoprotein gp120 have recently been reported. These antibodies, typified by VRC01, are remarkable for both their breadth and their potency. Crystal structures have revealed a common mode of binding for several of these antibodies; however, the precise relationship among CD4bs antibodies remains to be defined. Here we analyze existing structural and sequence data, propose a set of signature features for potent VRC01-like (PVL) antibodies, and verify the importance of these features by mutagenesis. The signature features explain why PVL antibodies derive from a single germ-line human VH gene segment and why certain gp120 sequences are associated with antibody resistance. Our results bear on vaccine development and structure-based design to improve the potency and breadth of anti-CD4bs antibodies.Keywords
This publication has 45 references indexed in Scilit:
- Biochemically Defined HIV-1 Envelope Glycoprotein Variant Immunogens Display Differential Binding and Neutralizing Specificities to the CD4-binding SiteJournal of Biological Chemistry, 2012
- Progress in the rational design of an AIDS vaccinePhilosophical Transactions Of The Royal Society B-Biological Sciences, 2011
- Broad neutralization coverage of HIV by multiple highly potent antibodiesNature, 2011
- Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1Science, 2010
- Polysaccharide mimicry of the epitope of the broadly neutralizing anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycansGlycobiology, 2010
- Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: Implications for evasion of immune responses and design of vaccine immunogensBiochemical and Biophysical Research Communications, 2009
- Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine TargetScience, 2009
- A method for identification of HIV gp140 binding memory B cells in human bloodJournal of Immunological Methods, 2009
- IMGT(R), the international ImMunoGeneTics information system(R)Nucleic Acids Research, 2008
- IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysisNucleic Acids Research, 2008