Epitopes described in "Structure of a clade C HIV-1 gp120 bound to CD4 and CD4-induced antibody reveals anti-CD4 polyreactivity."

Reference
Article Authors:Ron Diskin; Paola M Marcovecchio; Pamela J Bjorkman
Article Title:Structure of a clade C HIV-1 gp120 bound to CD4 and CD4-induced antibody reveals anti-CD4 polyreactivity.
Reference Detail
Reference ID:1019672
Abstract:Strategies to combat HIV-1 require structural knowledge of envelope proteins from viruses in HIV-1 clade C, the most rapidly spreading subtype in the world. We present a crystal structure containing a clade C gp120 envelope. The structure, a complex between gp120, the host receptor CD4 and the CD4-induced antibody 21c, reveals that the 21c epitope involves contacts with gp120, a nonself antigen, and with CD4, an autoantigen. Binding studies using wild-type and mutant CD4 show that 21c Fab binds CD4 in the absence of gp120, and that binding of 21c to clade C and HIV-2 gp120s requires the crystallographically observed 21c-CD4 interaction. Additional binding data suggest a role for the gp120 V1V2 loop in creating a high-affinity, but slow-forming, epitope for 21c after CD4 binds. These results contribute to a molecular understanding of CD4-induced antibodies and provide the first visualization to our knowledge of a potentially autoreactive antibody Fab complexed with both self and nonself antigens.
Date:2010
Reference Type:Literature
PubMed ID:20357769
Journal:Nat Struct Mol Biol
Journal Volume:17
Article Pages:608-13
Journal ISSN:1545-9985
Article Chemical List:Antibodies, Viral;Antigens, CD4;Epitopes;HIV Envelope Protein gp120
Article MeSH List:Antibodies, Viral(chemistry; immunology); Antigens, CD4(chemistry; immunology); Cell Line; Crystallography, X-Ray; Epitopes(chemistry; immunology); HIV Envelope Protein gp120(chemistry; immunology); HIV Infections(immunology); HIV-1(chemistry; immunology); Humans; Models, Molecular
Curation Last Updated:2014-07-16 22:33:33